Risk factors for highly pathogenic avian influenza in commercial layer chicken farms in Bangladesh During 2011

postprintA case control study was conducted during 2011 involved 90 randomly selected commercial layer farms infected with highly pathogenic avian influenza type A subtype H5N1 (HPAI) and 175 control farms randomly selected from within 5km of infected farms. A questionnaire was designed to obtain information about potential risk factors for contracting HPAI and was administered to farm owners or managers. Logistic regression analyses were conducted to identify significant risk factors. A total of 20/43 risk factors for contracting HPAI were identified after univariable logistic regression analysis. A multivariable logistic regression model was derived by forward stepwise selection. Both unmatched and matched analyses were done. The key risk factors identified were numbers of staff, frequency of veterinary visits, presence of village chickens roaming on the farm and staff trading birds. Aggregating these findings with those from other studies resulted in a list of 16 key risk factors identified in Bangladesh. Most of these related to biosecurity. It is considered feasible for Bangladesh to achieve a very low incidence of HPAI. Using the cumulative list of risk factors to enhance biosecurity pertaining to commercial farms would facilitate this objective. Key words: Avian influenza; case-control study; logistic regression; risk factors, observational studies

Risk factors for highly pathogenic avian influenza in commercial layer chicken farms in Bangladesh During 2011

A case control study was conducted during 2011 involved 90 randomly selected commercial layer farms infected with highly pathogenic avian influenza type A subtype H5N1 (HPAI) and 175 control farms randomly selected from within 5km of infected farms. A questionnaire was designed to obtain information about potential risk factors for contracting HPAI and was administered to farm owners or managers. Logistic regression analyses were conducted to identify significant risk factors. A total of 20/43 risk factors for contracting HPAI were identified after univariable logistic regression analysis. A multivariable logistic regression model was derived by forward stepwise selection. Both unmatched and matched analyses were done. The key risk factors identified were numbers of staff, frequency of veterinary visits, presence of village chickens roaming on the farm and staff trading birds. Aggregating these findings with those from other studies resulted in a list of 16 key risk factors identified in Bangladesh. Most of these related to biosecurity. It is considered feasible for Bangladesh to achieve a very low incidence of HPAI. Using the cumulative list of risk factors to enhance biosecurity pertaining to commercial farms would facilitate this objective. Key words: Avian influenza; case-control study; logistic regression; risk factors, observational studies

The Role of the Mucus Barrier in Digestion

Mucus forms a protective layer across a variety of epithelial surfaces. In the gastrointestinal (GI) tract, the barrier has to permit the uptake of nutrients, while excluding potential hazards, such as pathogenic bacteria. In this short review article, we look at recent literature on the structure, location, and properties of the mammalian intestinal secreted mucins and the mucus layer they form over a wide range of length scales. In particular, we look at the structure of the gel-forming glycoprotein MUC2, the primary intestinal secreted mucin, and the influence this has on the properties of the mucus layer. We show that, even at the level of the protein backbone, MUC2 is highly heterogeneous and that this is reflected in the networks it forms. It is evident that a combination of charge and pore size determines what can diffuse through the layer to the underlying gut epithelium. This information is important for the targeted delivery of bioactive molecules, including nutrients and pharmaceuticals, and for understanding how GI health is maintained

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Can adverse maternal and perinatal outcomes be predicted when blood pressure becomes elevated? Secondary analyses from the CHIPS (Control of Hypertension In Pregnancy Study) randomized controlled trial.

INTRODUCTION: For women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes. MATERIAL AND METHODS: This was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight <10th percentile) or maternal outcomes (severe hypertension, preeclampsia, or delivery at <34 or <37 weeks). A model containing all candidate predictors was used to start the stepwise regression process based on goodness of fit as measured by the Akaike information criterion. For face validity, these variables were forced into the model: treatment group ("less tight" or "tight" control), antihypertensive type at randomization, and blood pressure within 1 week before randomization. Continuous variables were represented continuously or dichotomized based on the smaller p-value in univariate analyses. An area-under-the-receiver-operating-curve (AUC ROC) of ≥0.70 was taken to reflect a potentially useful model. RESULTS: Point estimates for AUC ROC were <0.70 for all but severe hypertension (0.70, 95% CI 0.67-0.74) and delivery at <34 weeks (0.71, 95% CI 0.66-0.75). Therefore, no model warranted further assessment of performance. CONCLUSIONS: CHIPS data suggest that when women with chronic hypertension develop an elevated blood pressure in pregnancy, or formerly normotensive women develop new gestational hypertension, maternal and current pregnancy clinical characteristics cannot predict adverse outcomes in the index pregnancy

Successful treatment of bilateral open calcaneal fractures with concomitant lower extremity injuries: A case report

Open calcaneal fractures are high morbidity injuries and the risk of complications depends on the concomitant injuries, on the size and the position of the traumatic wound. A 53-year-old male patient with bilateral open calcaneal fractures and associated concomitant lower extremity injuries such as subtalar dislocation, talonavicular dislocation and open distal tibial metaphyseal fracture was immediately operated by percutaneous Kirschner wire fixation combined with external fixators. He was able to walk with full weight bearing without any assistance at the end of the first postoperative year. Early aggressive debridement and irrigation followed by fixation with percutaneous Kirschner wires and external fixator can supply bony alignment in open comminuted calcaneal fractures associated with concomitant lower extremity injuries and should be considered for the healthy and active patients before primary arthrodesis

Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency

The Cost Implications of Less Tight Versus Tight Control of Hypertension in Pregnancy (CHIPS Trial).

The CHIPS randomized controlled trial (Control of Hypertension in Pregnancy Study) found no difference in the primary perinatal or secondary maternal outcomes between planned "less tight" (target diastolic 100 mm Hg) and "tight" (target diastolic 85 mm Hg) blood pressure management strategies among women with chronic or gestational hypertension. This study examined which of these management strategies is more or less costly from a third-party payer perspective. A total of 981 women with singleton pregnancies and nonsevere, nonproteinuric chronic or gestational hypertension were randomized at 14 to 33 weeks to less tight or tight control. Resources used were collected from 94 centers in 15 countries and costed as if the trial took place in each of 3 Canadian provinces as a cost-sensitivity analysis. Eleven hospital ward and 24 health service costs were obtained from a similar trial and provincial government health insurance schedules of medical benefits. The mean total cost per woman-infant dyad was higher in less tight versus tight control, but the difference in mean total cost (DM) was not statistically significant in any province: Ontario ($30 191.62 versus$24 469.06; DM $5723, 95$296 to $12 272; P=0.0725); British Columbia ($30 593.69 versus $24 776.51; DM$5817; 95% confidence interval, -$385 to$12 349; P=0.0725); or Alberta ($31 510.72 versus$25 510.49; DM $6000.23; 95$154 to $12 781; P=0.0637). Tight control may benefit women without increasing risk to neonates (as shown in the main CHIPS trial), without additional (and possibly lower) cost to the healthcare system. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01192412

The elusive archaeology of Kongo urbanism: the case of Kindoki, Mbanza Nsundi (Lower Congo, DRC)

We present here results, analyses and an in-depth historical contextualisation of the fieldwork undertaken in 2012 and 2013 at the Kindoki site in the Lower Congo (DRC). This site is linked with Mbanza Nsundi, one of the Kongo Kingdom's provincial capitals, which turns out to be archaeologically 'elusive'. Pinpointing its location proved to be particularly challenging. To this end, a historically-informed excavation methodology was developed that was never implemented in Central Africa before. We combined a strategy of systematic test pits with a large-scale 50 m grid approach. A cemetery was identified on Kindoki Hill with distinct but contemporaneous quarters of a 16th-17thcenturies settlement on both sides. The cemetery itself contains mainly 18th-century burials, in all likelihood of successive Nsundi rulers. The foreign, especially Portuguese, ceramics excavated on the hilltop and the hundreds of Venetian and likely Bavarian beads found in the graves are indicative of Mbanza Nsundi's connection to trade routes linking the Atlantic coast with the Pool region. The most striking discovery is that of a previously unknown type of comb-impressed pottery, from a pit with a calibrated radiocarbon date AD 1294-1393 (2 sigma). This suggests that a settlement had been developing at Kindoki since at least the 14th century, which allows us, for the very first time, to spatially bridge Kongo history and 'prehistory'. For the entire Lower Congo region only three 14C dates posterior to AD 1000 were available before the start of the KongoKing project, twelve have been added for just Kindoki

Effects of bromopride on the healing of left colon anastomoses of rats

Objetivo: Avaliar os efeitos da bromoprida sobre a formação de aderências e a cicatrização de anastomoses de cólon esquerdo de ratos. Métodos: Foram incluídos 40 ratos, divididos em dois grupos contendo 20 animais, para administração de bromoprida (grupo de estudo- E) ou solução fisiológica (grupo controle- C). Cada grupo foi dividido em subgrupos contendo 10 animais cada, para eutanásia no terceiro (E3 e C3) ou no sétimo dia (E7 e C7) de pós-operatório. Os ratos foram submetidos à secção do cólon esquerdo e anastomose término-terminal. No dia da relaparotomia, foi avaliada a quantidade total de aderências e removido um segmento colônico contendo a anastomose para análise histopatológica, da força de ruptura e da concentração de hidroxiprolina. Resultados: Não houve diferença entre os grupos em relação à evolução clínica. Dois animais do grupo de estudo apresentaram deiscência de anastomose bloqueada. Os animais que receberam bromoprida apresentaram número de aderências intracavitárias e aderências à anastomose semelhantes ao grupo controle. As anastomoses dos animais do grupo E3 apresentaram menor resistência de ruptura do que as do grupo C3 (p=0,04). Este efeito não ocorreu no sétimo dia de pós-operatório (p=0,37). Não houve diferença significativa entre os grupos em relação à histopatologia ou concentração de hidroxiprolina das anastomoses. Conclusão: O uso da bromoprida está associado à diminuição da resistência tênsil de anastomoses do cólon esquerdo de ratos no terceiro dia de pós-operatório.Objective: To evaluate the effects of bromopride on the formation of adhesions and anastomotic healing in the left colon of rats. Methods: We divided 40 rats into two groups of 20 animals, administration of bromopride (study group-E) or saline (control group- C). Each group was divided into subgroups containing 10 animals each for euthanasia in the third (C3 and E3) or the seventh (E7 and C7) postoperative days. The rats were submitted to section of the left colon and end-to-end anastomosis. On the day of reoperation, we evaluated the total amount of adhesions and removed a colonic segment containing the anastomosis for histopathological analysis, assessment of rupture strength and hydroxyproline concentration. Results: There was no difference between groups in relation to clinical outcome. Two animals in the study group had blocked anastomotic leakage. The animals that received bromopride had the number of intracavitary adhesions and adhesions to the anastomosis similar to the control group. The anastomoses from the group E3 animals showed lower resistance to rupture the one from the C3 group (p = 0.04). This effect did not occur on the seventh postoperative day (p = 0.37). There was no significant difference between groups in relation to histopathology and hydroxyproline concentration in the anastomoses. Conclusion: The use of bromopride was associated with decreased tensile strength of left colon anastomosis in rats in the third postoperative day