Productive performance of beef cows subjected to different nutritional levels in the third trimester of gestation.

In general, calf production occurs in less intensive systems. The limitation of nutrients during the gestation phase of beef cows can have negative impacts on the consequent productivity of females. Therefore, this study aimed to evaluate the effects of nutritional levels in the third trimester of pregnancy on the productive performance of beef cows kept in a natural pasture (NP). Eighty-three Charolais × Nelore cows were used, ranging in age from 4 to 12 years, which were divided according to their nutritional levels during the third trimester of pregnancy: NP, cows supplemented with 100% of their energy and protein requirements (SP100) and cows supplemented with 150% of their energy and protein requirements (SP150). The experimental design was completely randomized with three treatments and a varied number of repetitions. The SP100 and SP150 cows presented better body condition at calving (2.92 and 2.99 vs 2.81 points) and at the start of the breeding season (2.90 and 2.95 vs 2.80 points) than did NP cows. The nutritional level of the cows in the third trimester of gestation did not influence the blood metabolite concentrations. The plasma levels of albumin and total proteins were 3.11 and 8.18 g/dl, respectively. Glucose and cholesterol showed values of 74.96 and 166.50 mg/dl. The lowest concentration of blood metabolites was observed in the first postpartum weeks. The SP100 and SP150 cows showed faster follicular growth and, consequently, a higher percentage of females with ovulatory follicles at 21 days postpartum than did NP cows (45.68, 41.11, and 11.00%, respectively). The SP150 cows had a higher pregnancy rate (40.74%), total calf production (295.88 kg/cow), and consequently, offspring sale value. An increased nutritional level in the third trimester of pregnancy improves the postpartum metabolic condition and productive efficiency of beef cows kept on NP.

Características de carcaça e carne de novilhos Aberdeen Angus submetidos à castração cirúrgica ou imunológica / Carcass characteristics and meat of Aberdeen Angus steers submitted to surgical or immunological castration

Objetivou-se avaliar as características de carcaça e carne de novilhos Aberdeen Angus castrados cirurgicamente em duas idades ou imunocastrados com dois protocolos. Foram utilizados 48 bezerros, monitorados a partir do nascimento e desmamados, com idade e peso médio inicial de seis meses e de 160±16,54kg, respectivamente. Os animais foram distribuídos aleatoriamente nos seguintes tratamentos: castração cirúrgica ao nascer; castração cirúrgica ao desmame; imunocastração com três doses da vacina Bopriva® e imunocastração com quatro doses da vacina Bopriva®. O delineamento experimental utilizado foi o inteiramente ao acaso. Novilhos imunocastrados com três doses apresentaram maior quebra ao resfriamento e menor espessura de gordura ajustada para 100kg de carcaça fria que castrados cirurgicamente ao nascer (P<0,05). A imunocastração com três doses proporcionou incremento na participação de músculo, em relação às castrações cirúrgicas, mas reduziu a gordura em relação à castração cirúrgica ao nascimento (P<0,05). A relação músculo:osso foi superior nos imunocastrados com três doses em relação a castrados cirurgicamente no desmame (P<0,05). Apesar de variações na participação tecidual na carcaça, a castração imunológica mostrou-se viável em substituição à castração cirúrgica, não alterando os padrões qualitativos da carne.(AU)

The objective of this study was to evaluate the carcass and meat characteristics of Aberdeen Angus steers surgically castrated at two ages or immunocastrated with two protocols. Forty-eight calves we used, monitored from birth and weaned, with age and initial mean weight of six months and 160±16.54kg, respectively. The animals were randomly assigned to the following treatments: surgical castration at birth; surgical castration at weaning; immunocastration with three doses of the Bopriva ® vaccine and immunocastration with four doses of the Bopriva ® vaccine. The experimental design was completely randomized. Immunocastrated steers with three doses had a greater cooling break and lower fat thickness adjusted for 100kg of cold carcass than surgically castrated at birth (P< 0.05). Immunocastration with three doses provided an increase in muscle participation in relation to surgical castration but reduced fat in relation to surgical castration at birth (P< 0.05). The muscle:bone ratio was higher in the immunocastrated with three doses compared to surgically castrated at weaning (P< 0.05). Despite variations in tissue involvement in the carcass, the immunological castration proved to be viable to replace surgical castration, not changing the quality of the meat standards.(AU)

Trueperella bernardiae: an unusual cause of septic thrombophlebitis in an injection drug user.

The clinical spectrum of human disease caused by Trueperella bernardiae is poorly described, partly as a result of historical difficulties with microbial identification. With the introduction of powerful new technologies, such as matrix-assisted desorption ionization-time of flight mass spectrometry, into routine microbiology laboratories, new insights into diseases caused by such organisms are being made. Here we report a case of septic thrombophlebitis with bacteraemia caused by this organism, together with a retrospective description of laboratory isolation of this organism over a period of 6 years in a hospital in London, UK.

Antistaphylococcal ß-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis.

The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal ß-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%; P = 0.27), 6-month mortality (31.6% versus 25.9%; P = 0.58), and survival time after discharge (P = 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7; P = 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.

The selective outpatient treatment of adults with imported falciparum malaria: a prospective cohort study.

BACKGROUND: Current UK malaria treatment guidelines recommend admission for all patients diagnosed with falciparum malaria. However, evidence suggests that certain patients are at lower risk of severe malaria and death and may be managed as outpatients. AIM: To prospectively assess the risk of post-treatment severe falciparum malaria in selected cases managed as outpatients. The readmission rate and treatment tolerability were assessed as secondary outcomes. DESIGN: Prospective cohort study. METHODS: Adults (>15 years old) diagnosed with falciparum malaria between May 2008 and July 2012 were selected for outpatient treatment using locally defined clinical and laboratory indicators based on known risk factors for severity and death. Treatment outcomes were assessed in clinic or by telephone 4-6 weeks after treatment. RESULTS: 269 adults were diagnosed with falciparum malaria on blood film between May 2008 and July 2012. Of 255 eligible participants, 106 patients were offered ambulatory treatment, of which 95 completed the study. The severe malaria rate was 0% (95% confidence interval (CI) 0-3.8%) and the readmission rate was 5.3% (95% CI 1.7-11.9) in the outpatient group. In addition, 10.6% (95% CI 5.2-18.7%) of outpatients reported drug-related side effects. CONCLUSIONS: The outpatient treatment of selected cases of falciparum malaria is effective in our high volume UK setting. We recommend adopting a similar approach to managing this infection in other non-endemic settings where immediate access to specialist advice is available.

Topoisomerase 2 Alpha Cooperates with Androgen Receptor to Contribute to Prostate Cancer Progression.

Overexpression of TOP2A is associated with risk of systemic progression in prostate cancer patients, and higher levels of TOP2A were found in hormone-resistant cases. To elucidate the mechanism by which high levels of TOP2A contribute to tumor progression we generated TOP2A overexpressing prostate cancer cell lines. We show that TOP2A promotes tumor aggressiveness by inducing chromosomal rearrangements of genes that contribute to a more invasive phenotype. Anti-androgen treatment alone was ineffective in killing TOP2A overexpressing cells due to activation of an androgen receptor network. TOP2A poisons killed tumor cells more efficiently early in the progression course, while at later stages they provided greater benefit when combined with anti-androgen therapy. Mechanistically, we find that TOP2A enhances androgen signaling by facilitating transcription of androgen responsive genes, thereby promoting tumor cell growth. These studies revealed a relationship between TOP2A and androgen receptor signaling pathway that contributes to prostate cancer progression and confers sensitivity to treatments.

ASCL1 and RET expression defines a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation.

ASCL1 is an important regulatory transcription factor in pulmonary neuroendocrine (NE) cell development, but its value as a biomarker of NE differentiation in lung adenocarcinoma (AD) and as a potential prognostic biomarker remains unclear. We examined ASCL1 expression in lung cancer samples of varied histologic subtype, clinical outcome and smoking status and compared with expression of traditional NE markers. ASCL1 mRNA expression was found almost exclusively in smokers with AD, in contrast to non-smokers and other lung cancer subtypes. ASCL1 protein expression by immunohistochemical (IHC) analysis correlated best with synaptophysin compared with chromogranin and CD56/NCAM. Analysis of a compendium of 367 microarray-based gene expression profiles in stage I lung adenocarcinomas identified significantly higher expression levels of the RET oncogene in ASCL1-positive tumors (ASCL1(+)) compared with ASCL1(-) tumors (q-value <10(-9)). High levels of RET expression in ASCL1(+) but not in ASCL1(-) tumors was associated with significantly shorter overall survival (OS) in stage 1 (P=0.007) and in all AD (P=0.037). RET protein expression by IHC had an association with OS in the context of ASCL1 expression. In silico gene set analysis and in vitro experiments by ASCL1 shRNA in AD cells with high endogenous expression of ASCL1 and RET implicated ASCL1 as a potential upstream regulator of the RET oncogene. Also, silencing ASCL1 in AD cells markedly reduced cell growth and motility. These results suggest that ASCL1 and RET expression defines a clinically relevant subgroup of ∼10% of AD characterized by NE differentiation.

Genetic analysis of aquaporin-4 in neuromyelitis optica.

OBJECTIVE: Autoantibodies to aquaporin-4 (AQP4) are specific and pathogenic for neuromyelitis optica (NMO). Therefore, we evaluated whether AQP4 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to NMO or whether mutations that potentially alter AQP4 structure or expression are present in some patients. METHODS: We genotyped 8 AQP4 SNPs chosen based on their minor allele frequency, location, and novelty in 177 NMO sporadic cases, 14 NMO familial cases, and 1,363 matched controls by TaqMan-based assay. We performed bidirectional sequencing of the promoter (1 kb), exons 0-4, and flanking splice consensus sequences, and the 5' and 3' untranslated regions of 177 sporadic and 14 familial NMO cases. RESULTS: One of 8 SNPs (minor allele frequency = 0.01) was associated with NMO (NC 18.8; chrom pos. 22695167: T>A): odds ratio (95% confidence interval) = 13.1 (1.4-126.7); p = 0.026. In 3 patients with NMO (2 related), we detected 2 different missense allelic mutations at Arg19 (R19I and R19T). None of the 1,363 control subjects had Arg19 mutations (p = 0.001). CONCLUSIONS: Except for one uncommon SNP, no tested SNP was associated with NMO, nor were 3 SNP haplotypes, providing no support for the hypothesis that genetic variation in AQP4 accounts for overall susceptibility to NMO. Two different allelic Arg19 missense mutations are specific to NMO and segregated with the disease in one pedigree. Although the pathobiology underlying this is not yet established, their effects on the structure of the M1 isoform N terminus or the regulatory sequence of the M23 isoform by virtue of their location support a role of AQP4 orthogonal array formation on molecular susceptibility to NMO.

Escherichia coli bacteraemia: how preventable is it?

Mandatory bacteraemia reporting was extended to include Escherichia coli from June 2011. The purpose of this study was to investigate whether the success seen in reducing meticillin-resistant Staphylococcus aureus infection rates could be duplicated with E. coli. All cases of E. coli bacteraemia occurring at our Trust in 2010 were reviewed. There were 216 episodes of E. coli bacteraemia, of which 63% were community-acquired. Only 19% had a potentially preventable cause identified, the majority (71%) of whom had urinary catheter-associated bacteraemia. These data must be kept in mind should targets to reduce E. coli bacteraemia be set in the future.

Permanent Genetic Resources added to the Molecular Ecology Resources Database 1 February 2010-31 March 2010.

This article documents the addition of 228 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Anser cygnoides, Apodemus flavicollis, Athene noctua, Cercis canadensis, Glis glis, Gubernatrix cristata, Haliotis tuberculata, Helianthus maximiliani, Laricobius nigrinus, Laricobius rubidus, Neoheligmonella granjoni, Nephrops norvegicus, Oenanthe javanica, Paramuricea clavata, Pyrrhura orcesi and Samanea saman. These loci were cross-tested on the following species: Apodemus sylvaticus, Laricobius laticollis and Laricobius osakensis (a proposed new species currently being described).

Pertussis outbreak on a neonatal unit: identification of a healthcare worker as the likely source.

We describe the investigation and containment of an outbreak of pertussis on a neonatal unit. Bacterial culture, polymerase chain reaction (PCR) and serology were used to confirm suspected cases. Two infants with pertussis were identified and a nurse with prolonged cough was traced as the likely source. Control interventions included mass chemoprophylaxis of healthcare workers and patients and exclusion from work of healthcare workers with cough. The use of PCR allowed rapid assessment of the extent of the outbreak. This outbreak highlights the risk to hospitalised infants posed by circulation of Bordetella pertussis in young adults and illustrates the utility of PCR in rapidly assessing the extent of outbreaks. Prevention strategies such as universal vaccination of adolescents, or selective vaccination of healthcare workers, should be considered in the UK.

Identification and control of an outbreak of ciprofloxacin-susceptible EMRSA-15 on a neonatal unit.

We report the identification and control of an outbreak of a ciprofloxacin-susceptible strain of UK epidemic meticillin-resistant Staphylococcus aureus (EMRSA)-15 on a neonatal unit (NNU). All babies were screened for MRSA on admission using ciprofloxacin-containing media which did not detect the outbreak strain. The first identified case was a premature baby who developed MRSA bacteraemia with associated tibial osteomyelitis and multiple subcutaneous abscesses. The outbreak strain was subsequently identified in the nasopharyngeal secretions of a second child who was not clinically infected. Screening of all patients on the NNU using non-ciprofloxacin-media identified two other colonised babies. All four patient isolates were EMRSA-15, spa type t022, SCCmec IV, Panton-Valentine leucocidin (PVL) negative, indistinguishable by pulsed-field gel electrophoresis and susceptible to all non-beta-lactam antimicrobials tested. The outbreak strain was cultured from four of 48 environmental sites in a communal milk-expressing room. Unsupervised movement of mothers to and from the milk-expressing room may have contributed to the outbreak. Control measures included cohort isolation of affected babies, improved environmental cleaning, increased emphasis on hand hygiene and education of mothers. Ciprofloxacin-containing media should be used with caution for MRSA screening in settings where ciprofloxacin-susceptible strains (including community-associated MRSA) are increasing in prevalence.

Non-bacterial infections in allogeneic non-myeloablative stem cell transplant recipients.

Data on non-bacterial infections during allogeneic non-myeloablative hematopoietic stem cell transplantation (HSCT) are widely different. We evaluated data on 48 consecutive patients who received a conditioning regimen with fludarabine and cyclophosphamide (73%) or fludarabine and total body irradiation (27%) and then underwent allogeneic non-myeloablative HSCT. Cytomegalovirus (CMV) infection was common and occurred in 48% of patients; 3 patients developed CMV disease, and all survived. CMV reactivation was found to be common with both conditioning regimens in our patient population. Invasive aspergillosis occurred in 4 patients (8%) and 3 died. Other serious non-bacterial infections were uncommon. Review of the available literature on non-myeloablative HSCT suggests that the frequency and type of opportunistic infections vary considerably.

Is antibiotic prophylaxis ever necessary before transoesophageal echocardiography?

Evidence strongly suggests that antibiotic prophylaxis should not be used routinely for transoesophageal echocardiography for any indication.

Recrudescence of imported falciparum malaria after quinine therapy: potential drug interaction with phenytoin.

Quinine remains a reliable treatment for falciparum malaria in most parts of the world. We report recrudescence of imported Plasmodium falciparum malaria following quinine treatment in the context of concurrent phenytoin use. Supported by a subtherapeutic quinine level, we hypothesise that a drug interaction with phenytoin may compromise the efficacy of quinine in the treatment of malaria.

Association of APOE polymorphisms with disease severity in MS is limited to women.

The authors studied the association of an exon 4 (E4*epsilon2/3/4) and three promoter polymorphisms of APOE with disease course and severity stratified by gender in 221 patients with multiple sclerosis from two overlapping population-based prevalence cohorts. Women carriers of the E4*epsilon2 allele took longer to attain an Expanded Disability Status Scale score of 6 (p = 0.015) and had more favorable ranked severity scores than noncarriers (p = 0.009). There was no association in men. Alleles epsilon3 or epsilon4 and promoter polymorphisms were not associated with disease course or severity.

Rifampin resistance in Mycobacterium kansasii is associated with rpoB mutations.

Rifampin is the most potent drug used in the treatment of disease due to Mycobacterium kansasii. A 69-bp fragment of rpoB, the gene that encodes the beta subunit of the bacterial RNA polymerase, was sequenced and found to be identical in five rifampin-susceptible clinical isolates of M. kansasii. This sequence showed 87% homology with the Mycobacterium tuberculosis gene, with an identical deduced amino acid sequence. In contrast, missense mutations were detected in the same fragment amplified from five rifampin-resistant isolates. A rifampin-resistant strain generated in vitro also harbored an rpoB gene missense mutation that was not present in the parent isolate. All mutations detected (in codons 513, 526, and 531) have previously been described in rifampin-resistant M. tuberculosis isolates. Rifampin MICs determined by E-test were <1 mg/liter for all rifampin-susceptible isolates and >256 mg/liter for all rifampin-resistant ones. In addition, four of the five rifampin-resistant isolates were also resistant to rifabutin. We have thus shown a strong association between rpoB gene missense mutations and rifampin resistance in M. kansasii. Although our results are derived from a small number of isolates and confirmation with larger numbers would be useful, they strongly suggest that mutations within rpoB form the molecular basis of rifampin resistance in this species.

High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: past or future?

Given that each year in the United States 180,000 new cases of breast cancer are diagnosed, with about 44,000 women succumbing to the disease, and that breast cancer is the second leading cause of cancer-related death in women, it is clear that existing therapy fails a large number of patients. Recently, a number of novel strategies have been developed in attempts to improve survival. These include agents used at very high dose requiring stem cell support. High-dose chemotherapy (HDC) with hematopoietic stem cell transplantation (HSCT), most frequently in the form of peripheral blood progenitor cell transplantation (PBPCT), is an highly active treatment approach in appropriate patients and the current data relating to this modality will be reviewed here. This article will attempt to place the recent randomized studies in perspective, to highlight the strengths and limitations of the data, and to offer some thoughts on future directions for the field.