Effect of prolactin concentration during the dry period on the subsequent milk production of dairy cows.

Shortening the dry period has a negative impact on milk production of the following lactation. One possible explanation is that a period of low prolactin (PRL) concentration is necessary to restore mammary gland milk production capacity. Therefore, the objective of this study was to determine the effect of lowering blood PRL level on subsequent lactation milk production. In this experiment, quinagolide was used to inhibit PRL secretion during the dry period. Thirty Holstein cows were randomly assigned one of 3 dry period managements: a conventional (60 d) dry period (CD) and 2 short (35 d) dry period treatments (SD). Short dry period cows received either water (SDwater) or quinagolide (2 mg, SDquin) injections twice daily from dry-off until 14 d before calving. Cows were followed during the first 20 wks of the subsequent lactation. When CD cows were dry but SD cows were lactating, concentration of PRL was lower in the CD cows than in the SD cows. During the injection period, PRL of SDquin cows was lower than that of the other treatments and was greater in the blood of SDwater than in that of CD cows. After the injection period until calving, no difference in PRL concentration was observed between treatments. After calving, PRL concentration of the SDquin cows was greater than those of CD and SDwater cows. During the first 20 wks of lactation, energy corrected milk (ECM) was lower in SDwater cows than in CD and SDquin cows. The ECM of the latter groups were not different. During the same period, mammary expression of genes related to milk synthesis, pro-apoptotic genes, as well as the expression of the short and long isoforms of the PRLR genes were not affected; however, the expression of SOCS3 gene tended to be lower for the SDquin than the SDwater cows. Lowering the PRL level during short dry period restored milk production to the level normally observed after a conventional dry period, which suggests that higher PRL levels during short dry period are the cause of the lower milk production after a short dry period. Ultimately, strategies to lower blood PRL level may help the adoption of short dry period.

Mechanism underlying the modulation of milk production by incomplete milking.

Mammary gland secretory activity is modulated by systemic and local factors; however, the relationship between these factors is unknown. The aim of this study was to determine how a local factor, such as incomplete milking, affects mammary epithelial cell activity, number, and responsiveness to blood prolactin (PRL). Eight cows in mid-lactation were differentially milked (i.e., their right quarters were milked incompletely at approximately 70%, and their left quarters were milked completely, twice daily for 4 wk). Throughout the experiment, milk yield was measured at the quarter level. Milk samples were collected from each quarter once a week to assess the milk components, and epithelial cell concentrations, as well as to isolate milk fat globule RNA. In the weeks before and after the experiment, mammary gland functional capacity was evaluated by measuring the volume of milk harvested after complete filling of the gland. At the end of the last experimental week, mammary gland biopsies were performed on each rear quarter. The milk production of quarters milked completely remained stable during the treatment period, whereas, as expected, the milk production of quarters milked incompletely was only 53% of completely milked quarters at the end of the period. Accordingly, the expression of genes related to milk synthesis (CSN2, LALBA, and ACACA) in milk fat was lower in the quarters that were milked incompletely. Incomplete milking decreased the milk lactose content, indicating a loss of integrity of tight junctions. The total yield of epithelial cells in milk was not affected, but their concentration in milk, the BAX:BCL2 gene expression ratio, and the loss of mammary functional capacity were greater in the quarters milked incompletely, suggesting an acceleration of involution in those quarters. The expression of the short isoform of the PRL receptor gene (PRLR) tended to be lower, and the expression of STAT5A and STAT5B tended to decline in the quarters milked incompletely. In mammary gland biopsy samples, the number of both short and long isoforms of the PRLR were not affected, nor were the amount and activation of STAT3 and STAT5. However, the ratio of PRLR short isoform to PRLR long isoform was lower in the quarters milked incompletely. The decrease in milk yield induced by incomplete milking is rapid and associated with a decrease in mammary epithelial cell activity and a decrease in the number of secretory epithelial cells. The results of this experiment provide only limited support for the hypothesis that modulation of the mammary gland's responsiveness to PRL is part of the mechanism by which local factors, such as incomplete milking, modulate milk synthesis.

Is cestode infection intensity associated with decreased body condition in the Eurasian woodcock Scolopax rusticola?

The Eurasian woodcock Scolopax rusticola is a widespread woodland specialist and a widely harvested quarry species throughout its European wintering areas, including Britain. Woodcock are prone to cestodiasis, but prevalence levels and possible effects on body condition remain under-studied. We studied the prevalence, abundance and intensity of cestodiasis in 161 woodcock harvested in four British regions in December and January during two consecutive winters (2013/14 and 2014/15). Cestodiasis prevalence was 90%, and there was no difference in prevalence between birds harvested in Cornwall, Wessex, East Anglia and Scotland. High prevalence levels were explained by the fact that earthworms (Lumbricidae) are intermediate hosts for some cestode species and also the most important dietary component of woodcock. The distribution of cestodiasis in woodcock was aggregated, such that when using the total length of cestodes per sample to measure abundance, 65% of the birds had less than 80 cm. Cestodiasis abundance varied between sexes across regions but the intensity was not affected by region, sex, age or their interactions. The intensity of cestodiasis was positively correlated with fresh weight and pectoral mass, while no significant correlation was found with the abdominal fat pad. Our results suggest that, despite high prevalence levels and intensity of cestodiasis in woodcock, host body condition is not significantly affected and hence it is unlikely that cestodiasis has a major effect on woodcock population dynamics.

Shape coexistence in the neutron-deficient even-even (182-188)Hg isotopes studied via coulomb excitation.

Coulomb-excitation experiments to study electromagnetic properties of radioactive even-even Hg isotopes were performed with 2.85 MeV/nucleon mercury beams from REX-ISOLDE. Magnitudes and relative signs of the reduced E2 matrix elements that couple the ground state and low-lying excited states in Hg182-188 were extracted. Information on the deformation of the ground and the first excited 0+ states was deduced using the quadrupole sum rules approach. Results show that the ground state is slightly deformed and of oblate nature, while a larger deformation for the excited 0+ state was noted in Hg182,184. The results are compared to beyond mean field and interacting-boson based models and interpreted within a two-state mixing model. Partial agreement with the model calculations was obtained. The presence of two different structures in the light even-mass mercury isotopes that coexist at low excitation energy is firmly established.

Steatitis in wild sharptooth catfish, Clarias gariepinus (Burchell), in the Olifants and lower Letaba Rivers in the Kruger National Park, South Africa.

Large numbers of adult Nile crocodiles, Crocodylus niloticus (Laurenti), died from pansteatitis during autumn and winter 2008 in the lower Letaba and Olifants River gorge in the Kruger National Park, South Africa. Consequently, the health status of fish from these waters was investigated. The study presents the pathological findings in fish inhabiting these rivers within the boundaries of the Park. Changes typical of steatitis were diagnosed in many of the larger specimens of sharptooth catfish, Clarias gariepinus (Burchell), caught within the Olifants River gorge. These fish carried large amounts of mesenteric fat with characteristic small brown granulomata within the adipose tissue. Necrosis and inflammation of the adipose tissues, with characteristic ceroid accumulation within the resultant granulomata and the associated aggregation of ceroid-containing macrophages, were demonstrated histologically and were typical of steatitis. Other changes included mild thickening and pallor of the gill tissues and swollen, orange, fatty livers. Focal hepatic lipidosis was demonstrated histologically, and special stains revealed storage of large amounts of iron in the livers. Blood smears revealed chromatin clumping in erythrocyte nuclei and nuclear and cell membrane irregularities. This is the first record of steatitis in wild-caught C. gariepinus.

Acute intermittent porphyria and chronic renal failure.

Despite the little known association between renal damage and the acute porphyrias, limited information is available on the characteristics and pathogenesis of renal disease in this patient group. Previous reports have focused on hypertension as the principal etiological factor. We have studied a series of 9 patients with acute intermittent porphyria (AIP) attending the Porphyria Clinic at King's College Hospital, London, UK, who were referred to the Renal Unit for investigation and treatment of their renal disease. No evidence of a glomerular lesion was found in any of the patients. In contrast, renal histology showed features of a tubulointerstitial disease, and there was evidence of impaired erythropoietin production. Hypertension and nonsteroidal antiinflammatory drug use were present in about a half of the patients. It is postulated that the nephrotoxic effects of porphyrin precursors may contribute to the etiology of this clinical syndrome.

The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist.

BACKGROUND: ADP-L-glycero--mannoheptose 6-epimerase (AGME) is required for lipopolysaccharide (LPS) biosynthesis in most genera of pathogenic and non-pathogenic Gram-negative bacteria. It catalyzes the interconversion of ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose, a precursor of the seven-carbon sugar L-glycero-mannoheptose (heptose). Heptose is an obligatory component of the LPS core domain; its absence results in a truncated LPS structure resulting in susceptibility to hydrophobic antibiotics. Heptose is not found in mammalian cells, thus its biosynthetic pathway in bacteria presents a unique target for the design of novel antimicrobial agents. RESULTS: The structure of AGME, in complex with NADP and the catalytic inhibitor ADP-glucose, has been determined at 2.0 A resolution by multiwavelength anomalous diffraction (MAD) phasing methods. AGME is a homopentameric enzyme, which crystallizes with two pentamers in the asymmetric unit. The location of 70 crystallographically independent selenium sites was a key step in the structure determination process. Each monomer comprises two domains: a large N-terminal domain, consisting of a modified seven-stranded Rossmann fold that is associated with NADP binding; and a smaller alpha/beta C-terminal domain involved in substrate binding. CONCLUSIONS: The first structure of an LPS core biosynthetic enzyme leads to an understanding of the mechanism of the conversion between ADP-D-glycero--mannoheptose and ADP-L-glycero-D-mannoheptose. On the basis of its high structural similarity to UDP-galactose epimerase and the three-dimensional positions of the conserved residues Ser116, Tyr140 and Lys144, AGME was classified as a member of the short-chain dehydrogenase/reductase (SDR) superfamily. This study should prove useful in the design of mechanistic and structure-based inhibitors of the AGME catalyzed reaction.

A strategy for monitoring and evaluating massive open online courses.

We argue that the complex, innovative and adaptive nature of Massive Open Online Course (MOOC) initiatives poses particular challenges to monitoring and evaluation, in that any evaluation strategy will need to follow a systems approach. This article aims to guide organizations implementing MOOCs through a series of steps to assist them in developing a strategy to monitor, improve, and judge the merit of their initiatives. We describe how we operationalise our strategy by first defining the different layers of interacting agents in a given MOOC system. We then tailor our approach to these different layers. Specifically, a two-pronged approach was developed, where we suggest that individual projects be assessed through performance monitoring; assessment criteria for which would be defined at the outset to include coverage, participation, quality and student achievement. In contrast, the success of an overall initiative should be considered within a more adaptive, emergent evaluation inquiry framework. We present the inquiry framework we developed for MOOC initiatives, and show how this framework might be used to develop evaluation questions and an assessment methodology. We also define the more fixed indicators and measures for project performance monitoring. Our strategy is described as it was developed to inform the evaluation of a MOOC initiative at the University of Cape Town (UCT), South Africa.

Hospital care by hospital-based and clinic-based faculty: a prospective, controlled trial.

BACKGROUND: The hospital length of stay decreases and clinical outcomes are maintained when teaching hospitals involve hospital-based attending physicians in comparison with traditional attending physicians. The attending physician's time commitment, including the number of hours per day and months per year, required to achieve this result is unknown. This study compared the clinical outcomes and cost of care for patients treated by hospital-based and clinic-based attending physicians devoting dramatically different amounts of time to supervising residents on the medical wards of a suburban county hospital. METHODS: Patients were alternately admitted to 2 groups of ward teams. Faculty who attended 10 months of the year supervised one group. The comparison group's attending physicians were on service for 2 months or less and maintained clinic responsibilities while on service. The cost of patient care was compared by means of the length of stay, total hospital costs, and costs for ancillary services. Hospital mortality and readmission rates compared clinical outcomes. RESULTS: There were 4456 patients hospitalized on the medical wards of a teaching service. No differences were detected in the length of stay (4.37 +/- 0.1 days for hospital-based and 4.39 +/- 0.1 days for clinic-based attending physicians). Hospital cost was observed to be similar (average cost, $5989 and $5977 per patient, respectively). The clinical outcomes were equivalent, with adjusted mortality rates for hospital-based attending physicians of 3.2% vs 3.9% for clinic-based attending physicians (P =.28). CONCLUSION: An increase of faculty time and involvement for supervision of resident-managed hospital care did not improve clinical outcomes or decrease costs during the 1-year study period.

Bullous dermatoses in end-stage renal failure: porphyria or pseudoporphyria?

Bullous dermatoses (BD) are well recognized in patients with end-stage renal disease (ESRD). It is important to distinguish pseudoporphyria (porphyrin accumulation due to decreased clearance) from true porphyrias, particularly those in which acute neurological attacks may occur. Investigation of the dialysis patient poses practical diagnostic difficulties because urinary porphyrin profiles are not available. We describe a patient on continuous ambulatory peritoneal dialysis (CAPD) with several recognized causative factors for porphyria cutanea tarda (PCT). The patient presented with a blistering photosensitive rash. We highlight the importance of investigating anuric patients with fractionation of both fecal and plasma porphyrins. Plasma porphyrins were grossly elevated (345 nmol/L; reference range, <13), whereas plasma porphyrins in a control group of CAPD patients without blistering rashes were only minimally elevated (mean, 23.9 nmol/L; SD, 11.0; n = 9). Fractionation of fecal porphyrins by high-performance liquid chromatography (HPLC) yielded a pattern typical of PCT. In addition to the contributory factors for PCT that were present, it is possible that porphyrin accumulation secondary to renal failure played a role in the expression of her disease. Patients with ESRD presenting with BD require careful evaluation, including fractionation of fecal porphyrins.

Estimations of serum arabinitol for diagnosing invasive candidosis.

Arabinitol concentrations were determined in 157 serum samples from 95 patients with suspected invasive candidosis and in 10 serum samples from healthy laboratory workers. Fifty eight of the 95 patients, subsequently diagnosed as not having invasive candidosis had concentrations of arabinitol below 1.2 micrograms/ml (mean 0.59 (SD) 0.26). Sera from the healthy laboratory workers gave similar results (mean 0.55 (0.05]. Concentrations above the normal range were found in 18 of the 19 cases of confirmed or probable invasive candidosis and in seven of eight patients with infected intravenous lines or cannulas and clinical evidence of systemic infection. Raised concentrations were also seen in 10 other patients, including nine with renal failure who did not have invasive infections. Multiple serum samples obtained from 33 patients showed that sequential estimations were of value for diagnosing a developing infection. Despite some difficulties of interpretation the technique is rapid and specific and is suitable for use in the diagnostic laboratory of a larger general hospital.

ACP Best Practice No 165: front line tests for the investigation of suspected porphyria.

The porphyrias are uncommon disorders of haem biosynthesis and their effective management requires prompt and accurate diagnosis. This article describes methods for the determination of urinary porphobilinogen, urinary and faecal total porphyrins, and total porphyrins in erythrocytes and plasma that are suitable for use in non-specialist laboratories. The selection and interpretation of these methods, and the indications for further, more specialised, investigation are discussed.

Gas-lipuid chromatographic analysis of metabolic products in the identification of bacteroidaceae of clinical interest.

The acid end-products of 185 isolates from the family Bacteroidaceae were separated and analysed by gas-liquid chromatography on broth cultures. Different media were evaluated and definitive studies were performed in a fully supplemented complex medium. The limitations of this approach to the identification of a wide range of strains from various clinical sources were determined and the results were compared with those of a series of morphological, biochemical, tolerance and antibiotic-resistance tests. All test strains were identified to generic level by simple microscopic and colonial observations and GLC analysis; additional tests were required to allow species or subspecies identification of most strains. Population differences were detected between some species or subspecies isolated from different clinical sites by quantitative analyses of fatty acids, but individual strains could not always be separated because of overlapping ranges of distribution of acids that were common products of more than one species or subspecies. Small differences in minor products between different species or subspecies were variable and are not considered adequate for discrimination at these taxonomic levels without support from other observations. The potential application of the GLC technique to the rapid and accurate identification of these organisms in hospital laboratories is considered.

A scheme for the identification of clinical isolates of Gram-negative anaerobic bacilli by conventional bacteriological tests.

More than 1000 strains of gram-negative anaerobic bacilli, including reference strains, clinical isolates, and members of the normal flora of the mouth, lower gastro-intestinal tract and vagina of healthy human subjects, were studied by conventional bacteriological methods and by gas-liquid chromatographic analysis of metabolic products in a series of investigations. A short combined set of tests with particular discriminant value was selected, and a scheme for the identification of the species and subspecies encountered in the diagnostic bacteriological laboratory was based upon our composite results. The tests are: antibiotic-disk resistance tests with neomycin 1000 micrograms, kanamycin 1000 micrograms, penicillin 2 units and rifampicin 15 micrograms per disk; tolerance tests with sodium taurocholate, Victoria blue 4R and gentian violet; and tests for pigment production, indole production, aesculin hydrolysis and the fermentation of glucose, lactose, sucrose, rhamnose, trehalose, mannitol and xylose. Gram-negative anaerobic bacilli are divided into four groups: (1) the fragilis group with nine species, which include the five subgroups previously classified as subspecies of B. fragilis; (2) the melaninogenicus-oralis group, which includes the three saccharolytic subspecies (ss.) of B. melaninogenicus--ss. melaninogenicus, ss. intermedius and ss. levii--and four non-pigmented species; (3) the asaccharolytic group, which comprises B. asaccharolyticus (formerly B. melaninogenicus ss. asaccharolyticus), B. corrodens and other non-pigmented non-saccharolytic strains, and (4) the fusobacteria.

Septicemia due to Yersinia pseudotuberculosis--a case report.

A case report is presented concerning Yersinia pseudotuberculosis septicemia presenting as an acute abdominal emergency in an elderly diabetic man with multiple medical problems.

International air travel: a risk factor for attacks in acute intermittent porphyria.

Five patients are reported with acute intermittent porphyria in whom attacks were apparently precipitated by international air travel. In four subjects this was the initial presenting attack and in a fifth the cause of an acute relapse in a patient requiring regular haem arginate prophylaxis. Multifactorial precipitants implicated include, dehydration, missed meals, alcohol use, infection, chronic hypoxia, premenstrual syndrome and stress. Acute intermittent porphyria should be suspected in individuals presenting with unexplained acute abdominal pain following international air travel. Appropriate precautions may reduce the incidence of attacks in known porphyrics.

Estimation of whole body bone resorption rate: a comparison of urinary total hydroxyproline excretion with two radioisotopic tracer methods in osteoporosis.

In 37 female patients with primary osteoporosis, urinary hydroxyproline excretion, determined in 18 24-h consecutive complete urine collections was compared with two radioisotopic measurements of bone resorption rate measured simultaneously using 85Sr. A somewhat better fit was obtained when the kinetically determined bone resorption rate was corrected for long-term exchange processes within bone. Regression analysis showed that the intercept of the regression of hydroxyproline excretion on resorption rate, corrected or uncorrected for exchange, was significantly higher than zero at about 100 mumol/day. This is consistent with a substantial fraction of urinary hydroxyproline arising from non-bony sources. Fifteen paired studies were analysed and the results suggested that intra-individual variability in these relationships (when studies were separated by a year or more) were similar to inter-individual variability. We calculated the precision with which an estimate of bone resorption could be determined based on the calculated regressions. As a means of non-invasive quantitation of whole body bone resorption rate, the excretion rate of hydroxyproline, measured over 5 days, for example, appeared competitive with isotopic methods making no correction for exchange and relatively little worse than our exchange corrected method.

Ill-conditioned Shake-and-Bake: the trap of the false minimum.

The alternation of phase refinement with the imposition of real-space constraints is the essence of the Shake-and-Bake procedure. Typically, these constraints prevent trial structures from falling into local minima. Nevertheless, P1 structures appear to migrate to false minima with significant frequency. These false minima are characterized by the presence of a large 'uranium' peak on the corresponding Fourier map. Fortunately, they can be recognized and avoided by considering the values of the minimal function both before and after the application of constraints. However, it appears that finding solutions for large P1 structures is likely also to require parameter-shift conditions different from those that have been found to work well in other space groups. In fact, these conditions often yield an unusually high percentage of solutions.

Performance of screening tests for porphyria.

The clinical utility of screening tests for porphyria has been assessed in 201 cases referred to Northwick Park Hospital. Routine screening in the referring laboratories was unreliable giving both false negative and positive results. Only 43% of porphyrics were correctly identified, apparently due to poor analytical sensitivity. Evidence is presented to show that the adoption of alternative semiquantitative tests for porphyrins employing spectrophotometric scanning of acidified urine or of faecal extracts will overcome many of these problems.

Identification of acute porphyria: evaluation of a commercial screening test for urinary porphobilinogen.

A commercial semi-quantitative kit (Trace) for urinary porphobilinogen (PBG) in which urine is pre-treated with ion-exchange resin and the colour of the Ehrlich-PBG adduct matched against a set of surrogate standards was compared with qualitative screening methods (Watson-Schwartz) in common use. Twenty samples in which PBG had been quantitated were blindly tested by both methods in each of 13 typical user laboratories. For urine samples with raised PBG, 123 out of 129 results were positive when tested with the Trace kit. Using qualitative tests routinely in use in the various laboratories only 45 out of 119 results were unequivocally positive. Sixteen out of 91 results for pigmented urine samples with normal PBG were reported as positive using qualitative screening tests, but only one using the Trace kit. Therefore, the Trace method is far more sensitive and specific than the qualitative screening tests. It is recommended that Watson-Schwartz-type screening tests should be abandoned and, ideally, all urine samples analysed by quantitative methods. However, the Trace method is a convenient alternative which is adequate for the initial screening of symptomatic patients.