Development of the Chick Microbiome: How Early Exposure Influences Future Microbial Diversity.

The concept of improving animal health through improved gut health has existed in food animal production for decades; however, only recently have we had the tools to identify microbes in the intestine associated with improved performance. Currently, little is known about how the avian microbiome develops or the factors that affect its composition. To begin to address this knowledge gap, the present study assessed the development of the cecal microbiome in chicks from hatch to 28 days of age with and without a live Salmonella vaccine and/or probiotic supplement; both are products intended to promote gut health. The microbiome of growing chicks develops rapidly from days 1-3, and the microbiome is primarily Enterobacteriaceae, but Firmicutes increase in abundance and taxonomic diversity starting around day 7. As the microbiome continues to develop, the influence of the treatments becomes stronger. Predicted metagenomic content suggests that, functionally, treatment may stimulate more differences at day 14, despite the strong taxonomic differences at day 28. These results demonstrate that these live microbial treatments do impact the development of the bacterial taxa found in the growing chicks; however, additional experiments are needed to understand the biochemical and functional consequences of these alterations.

Drug screening strategy for human membrane proteins: from NMR protein backbone structure to in silica- and NMR-screened hits.

About 8000 genes encode membrane proteins in the human genome. The information about their druggability will be very useful to facilitate drug discovery and development. The main problem, however, consists of limited structural and functional information about these proteins because they are difficult to produce biochemically and to study. In this paper we describe the strategy that combines Cell-free protein expression, NMR spectroscopy, and molecular DYnamics simulation (CNDY) techniques. Results of a pilot CNDY experiment provide us with a guiding light towards expedited identification of the hit compounds against a new uncharacterized membrane protein as a potentially druggable target. These hits can then be further characterized and optimized to develop the initial lead compound quicker. We illustrate such "omics" approach for drug discovery with the CNDY strategy applied to two example proteins: hypoxia-induced genes HIGD1A and HIGD1B.

Impact of HIV infection and exposure on survival in critically ill children who attend a paediatric emergency department in a resource-constrained setting.

OBJECTIVE: To assess the impact of HIV infection and exposure on survival in critically ill children requiring resuscitation. METHODS: A 6-month descriptive prospective cohort study of all live admissions to the resuscitation room of an urban paediatric emergency department in Blantyre, Malawi. RESULTS: 583 children were resuscitated, of whom 401 (69%) survived to hospital discharge. 26% of all children tested positive for HIV infection (152/576), and this was highest in patients presenting with shock (66%; 162/247), clinically diagnosed septicaemia (57%; 125/218) and malnutrition (40%; 24/60). Of 152 HIV-seropositive children, 30 (20%) died within 24 h, while among 424 seronegative children 36 (8.4%) died within 24 h (p<0.001). Later deaths (>24 h) were also more common in HIV-seropositive children compared with HIV-uninfected patients (24.3% vs 12.3%; p<0.001). Survival to 24 h was 80% (122/152) and to discharge 56% (85/152) in HIV-seropositive children. In HIV-uninfected children survival to 24 h was 92% (388/424) and to discharge 79% (336/424). CONCLUSION: Early and late case death rates are greater in HIV-seropositive than in HIV-uninfected children. 80% of HIV-infected children survived the period most influenced by the process of resuscitation, that is, the first 24 h. HIV status alone should not influence the limitation of intervention decisions in the resuscitation room when faced with a critically ill child.

Effects of antibiotics and oil on microbial profiles and fermentation in mixed cultures of ruminal microorganisms.

Ionophores and supplemental fat are fed to lactating cows to improve feed efficiency. Their effect on rumen fermentation is similar, but less is known about their impact on rumen microbes. The objective of this study was to determine the effects of monensin (M), bacitracin (B), and soybean oil (O) on microbial populations. Mixed cultures of rumen microbes were incubated in 5 dual-flow continuous fermentors and fed 13.8 g of alfalfa hay pellets daily (DM basis) for 16 d. All fermentors were allowed to stabilize for 4 d. From d 5 to 10, two fermentors received O (5% of diet DM), one fermentor received M (22 mg/kg), and one received B (22 mg/kg). From d 11 to 16, the 2 fermentors receiving O also received either M (OM) or B (OB) and O was included in the fermentors receiving M (MO) and B (BO). One fermentor served as the control and received 100% alfalfa pellets throughout the experiment. Each run was replicated 3 times. Samples were taken at 2 h after the morning feeding on d 4, 10, and 16 and were analyzed for bacterial populations using terminal restriction fragment length polymorphism. Volatile fatty acid concentration, methane production, and pH in the control cultures were not affected by time and remained similar during the entire experiment. The M and O treatments reduced molar concentration of acetate, increased concentration of propionate, and decreased methane production. Bacitracin did not alter acetate or propionate concentration, but reduced methane production. All 3 treatments (M, B, and O) altered the fragment patterns of microbial profiles. In contrast, treatments MO, OM, BO, and OB had little effect on culture fermentation despite differences in the patterns of microbial fragments. The terminal restriction fragment length polymorphism data suggest that microbial adaptation to the in vitro system in the control fermentor occurred within 4 d.

Characterization of Escherichia coli populations from gulls, landfill trash, and wastewater using ribotyping.

Due to their opportunistic and gregarious nature, gulls may be important reservoirs and vectors for anthropogenically derived fecal pathogens in coastal areas. We used ribotyping, a genotypic bacterial source tracking method, to compare populations of Escherichia coli among herring gulls Larus argentatus, great black-backed gulls L. marinus, wastewater, and landfill trash in New Hampshire and Maine, USA. Concentrations of E. coli in gull feces varied widely among individuals, but were generally high (6.0 x 10(1) to 2.5 x 10(9) g(-1) wet weight). Of 39 E. coli isolates from L. argentatus, 67% had banding patterns that were > or = 90% similar to those from wastewater and trash, whereas only 39% of 36 L. marinus isolates exhibited > or = 90% similarity to these sources. Strains of E. coli from gulls matched (> or = 90% similarity) more strains from wastewater (39% matching) than from trash (15% matching). E. coli isolates from L. marinus feces exhibited a greater diversity of banding patterns than did isolates from L. argentatus. There were more unique E. coli banding patterns in trash samples than in wastewater, and higher diversity indices in the former compared to the latter. These findings suggest that both species of gulls, especially L. argentatus, obtain fecal bacteria from wastewater and landfill trash, which they may transport to recreational beaches and waters. Our results also indicate that E. coli populations may vary widely between gull species, and between the anthropogenic habitats that they frequent, i.e. landfills and wastewater treatment facilities.

Introduction of HIV post-exposure prophylaxis for sexually abused children in Malawi.

AIMS: To improve the care of children who are victims of child sexual abuse (CSA) by routinely assessing eligibility for HIV post-exposure prophylaxis (PEP) and to investigate the feasibility, safety, and efficacy of such treatment started in a paediatric emergency department in Malawi. METHODS: Children presenting to the Queen Elizabeth Central Hospital, Blantyre between 1 January 2004 and 31 December 2004 with a history of alleged CSA were assessed for eligibility for HIV PEP and followed prospectively for six months. RESULTS: A total of 64 children presented with a history of alleged CSA in the 12 month period; 17 were offered PEP. The remainder were not offered PEP because of absence of physical signs of abuse (n = 20), delay in presentation beyond 72 hours from assault (n = 11), repeated sexual abuse in the preceding six months (n = 15), and HIV infection found on initial testing (n = 1). No family refused an HIV test. No side effects due to antiretroviral therapy were reported. Of the 17 children commenced on PEP, 11 returned for review after one month, seven returned at three months, and two of 15 returned at six months post-assault. None have seroconverted. CONCLUSIONS: In a resource-poor setting with a high HIV prevalence, HIV PEP following CSA is acceptable, safe, and feasible. HIV PEP should be incorporated in to national guidelines in countries with a high community prevalence of HIV infection.

Confidence of compliance: a Bayesian approach for percentile standards.

Rules for assessing compliance with percentile standards commonly limit the number of exceedances permitted in a batch of samples taken over a defined assessment period. Such rules are commonly developed using classical statistical methods. Results from alternative Bayesian methods are presented (using beta-distributed prior information and a binomial likelihood), resulting in "confidence of compliance" graphs. These allow simple reading of the consumer's risk and the supplier's risks for any proposed rule. The influence of the prior assumptions required by the Bayesian technique on the confidence results is demonstrated, using two reference priors (uniform and Jeffreys') and also using optimistic and pessimistic user-defined priors. All four give less pessimistic results than does the classical technique, because interpreting classical results as "confidence of compliance" actually invokes a Bayesian approach with an extreme prior distribution. Jeffreys' prior is shown to be the most generally appropriate choice of prior distribution. Cost savings can be expected using rules based on this approach.

Bounded hybrid superiority in an avian hybrid zone: effects of mate, diet, and habitat choice.

There has been considerable debate in the study of hybrid zones as to whether hybrids may be superior to parental types within the area of contact (bounded hybrid superiority). In birds, naturally occurring hybridization is relatively common, and hybridization within this group always involves mate choice. If hybrids are superior, females choosing heterospecific mates should be expected to show higher fitness under the conditions prevalent in the hybrid zone. Hybrid superiority under these circumstances would reduce reinforcement and thereby help to maintain the hybrid zone. To examine this issue, we studied reproductive performances of hybrids and parental species of gulls (Larus occidentalis and Larus glaucescens) at two colonies within a linear hybrid zone along the west coast of the United States. This hybrid zone contains predominantly gulls of intermediate phenotype. Previous studies indicated that hybrids were superior to one or both parental types, but provided no data on possible mechanisms that underlie this hybrid superiority. Using a hybrid index designed specifically for these species, we identified to phenotype more than 300 individuals associated with nests, including both individual males and females within 73 pairs in the central portion of the hybrid zone and 74 pairs in the northern portion of the hybrid zone. There was little evidence of assortative mating, and what little there was resulted solely because of pairings within intergrades. In the central hybrid zone, females paired with hybrid males produced larger clutches and hatched and fledged more chicks compared with females paired to western gull males. This was a result of heavy predation on eggs in sand habitat, where male western gulls established territories. In contrast, many hybrid males established territories in vegetated cover that was less vulnerable to predation. In the northern part of the hybrid zone, clutch size did not differ among pair categories, however, there were differences in hatching and fledging success, with females paired to hybrid males showing better success compared to females paired to glaucous-winged gull males. Hybrids showed better hatching and fledging success in the north because hybrids are more like western gulls than glaucous-winged gulls in foraging behavior, taking a higher percentage of fish in their diet, which enhances chick growth and survival. This is believed to be the first documentation of bounded hybrid superiority that delineates the mechanisms that underlie hybrid superiority.

A proposed model for telemedicine to supplement the physician workforce in the USA.

Maldistribution of physicians is the norm in much of the USA. This paper explores the effect that the integration of telemedicine into the health system could have on physician workforce requirements in the USA. The analysis is based on preliminary evidence suggesting that telemedicine is an effective and efficient means of delivering a broad spectrum of health services to medically under-served rural and inner-city communities. While the emphasis here is on interactive, video-based telemedicine services, other telemedicine modalities, such as store-and-forward techniques and remote monitoring, are likely to have a parallel effect. As these new technologies become a normal part of health care, they will reshape the medical workforce and exert a profound influence on physician workforce requirements in the USA. This paper presents a potential model for this reshaped workforce that emphasizes an expanded role for mid-level health-care providers.

Continuous effluent consents: Modelling and compliance testing.

The control of continuous polluting discharges in the U.K. was placed in a framework of statistically based legislation nearly 10 years ago. Both discharge standards and desired river quality class objectives are assessed within a probabilistic system of pollution control whereby a minimum level of 95 percent compliance with standards has to be achieved. The use of such a statistical framework permits occasional infringements of what would otherwise be fixed standards. This enables the Water Industry to manage river quality without undue risk of prosecution or unnecessary capital expenditure on effluent treatment.The change to a statistically based system has been a slow process carried out in stages: from the introduction of a river quality classification; setting long term river quality objectives; then setting discharge consents to achieve these objectives; and finally monitoring compliance with the consents and objectives. Each of these stages has required the development of the necessary statistical tools for river quality planning and management. Due to the decentralised nature of the currently catchment-based Water Authorities, several different statistical approaches have been adopted. However, if, as is planned for the near future, river quality management is carried out by a national regulatory body, then some rationalisation of current methodologies will have to be undertaken.This paper introduces and examines current U.K. approaches to river quality management and pollution control. Particular emphasis is placed on the statistical modelling techniques used for consent setting and compliance testing. Some of the commonly used techniques are compared and evaluated. A description is presented of work that is underway to develop a framework for the establishment and assessment of intermittent pollution control criteria.

Screening for hepatocellular carcinoma. Review and perspective.

In patients with hepatocellular carcinoma, early diagnosis offers the only hope for resection and cure. Data from Asia, where it is closely associated with viral hepatitis, indicate that serum alpha-fetoprotein assay and abdominal ultrasonography are the most effective and feasible screening tests. These data may not be applicable in America, where most patients at risk for hepatocellular carcinoma have underlying alcoholic cirrhosis. Also, it is unclear whether resecting "curable" lesions prolongs survival, particularly in patients with cirrhosis. Screening trials are indicated to answer these questions. Preventing risk factors, however, especially hepatitis B viral disease, is of paramount importance throughout the world.

Migration of Teflon after vocal cord injection.

Each of eight mongrel dogs received a 0.5 ml injection of polytef paste into the right vocal fold. These dogs were killed at 1 week, 1 month, 3 months, and 6 months after injection, and a number of organs were examined. Polarizing microscopy was used to examine the upper cervical lymph nodes, lower cervical lymph nodes, mediastinal lymph nodes, abdominal lymph nodes, cerebral cortex, brainstem, lung, liver, spleen, and kidney to determine if migration of polytef had occurred. Examination of these organs revealed that there was consistent migration of polytef particles into the cervical lymph nodes, with the highest incidence occurring in upper cervical lymph nodes on the side of injection. There was no evidence of migration of polytef particles to distant sites. The study shows that polytef particles may migrate to cervical lymph nodes after injection into the larynx; however, there is no evidence of distant migration.

Nerve grafting. Functional results after primary vs delayed repair.

The finding of heightened metabolic activity in nerve cell bodies after axonal injury has led to speculation that delaying motor nerve repair would be beneficial. Using a sciatic nerve model, 100 rats were grouped based on nerve autograft donor and recipient site variables. Animals were subjected to electrophysiologic testing at 3, 6, 9, and 12 weeks after grafting. Twitch force and nerve compound action potential parameters were calculated and compared using two-way analysis of variance. Previous studies have suggested interaction between donor and recipient variables. We cannot support these findings. Our data revealed no significant difference between immediate or delayed nerve repair or between fresh or predegenerated nerve grafts.

Generalized motor seizure following metrizamide cisternography.

Metrizamide is a water-soluble contrast medium used as a diagnostic tool in myelography and cisternography. Despite its accepted safety, its use has been associated with generalized motor seizures, and several cases of this toxicity have been reported. Risk factors include phenothiazine ingestion, seizure history, and large doses of the contrast material. Abnormal electroencephalographic wave patterns, as well as seizure activity, are less frequent after cisternography than myelography. A case of a metrizamide-induced generalized motor seizure following cisternography is reported in a patient with none of the above risk factors. The need for a thorough medication history and the use of prophylactic anticonvulsants in selected patients is discussed.

Animal model for peripheral nerve grafting.

We propose an animal model from which it is possible to follow nerve-muscle unit recovery after a nerve graft easily, consistently, and relatively inexpensively. The model is also compatible with subsequent histologic or histochemical analysis. We document the recovery of a group of animals after nerve grafting to demonstrate the flexibility of the model.

Tendon and pulleys at the metacarpophalangeal joint of a finger.

In fresh frozen traumatically amputated forearms with a constant tension of one kilogram on the flexor profundus tendon and the interphalangeal joints fixed in full extension by a Kirschner wire, the excursion of the tendon at the metacarpophalangeal joint and the force at the finger tip were correlated with different angles of flexion of the joint, first with the finger intact and then after varying amounts of advancement of the metacarpophalangeal joint pulley system. Pulley advancement increased the tendon excursion required to flex this joint and thus the mechanical advantage at this joint, but only when the joint was partly flexed. The extra excursion required at the metacarpophalangeal joint would be expected to weaken the interphalangeal joints at full flexion. Advancement also permitted ulnar-radial displacement of the tendon at the level of the metacarpophalangeal joint and hence could accentuate ulnar or radial drift. Pulley advancement is not recommended.

[Comprehensive lung function test for outpatients: a present-day review and its application]. / 'n omvattende Longfunksie-siftingstoets vir buitepasiënte: 'n huidige oorsig en die toepassing daarvan

A method for the measurement of recognised lung function parameters is described. Bedsides being useful for the detection of early pathology, the information obtained by this method is generally sufficient for an early diagnosis. A large number of patients can be examined per day and the test is also informative in high-risk pre-operative patients. Furthermore, the method is suitable for epidemiological studies and has already been used by the Medical Research Council to determine the incidence of chronic obstructive lung disease in the Bellville area.

Attempts to transfer immunity to Trichobilharzia ocellata (Trematoda: Schistosomatidae) passively via lymphoid cells and/or serum.

White Pekin ducklings were injected with serum, lymphoid cells, or both, derived from donor birds which were immune to reinfection by the schistosome trematode, Trichobilharzia ocellata. Ducklings receiving serum and/or cells from susceptible birds, and untreated ducklings, served as controls. One set of experimental and control ducklings was kept alive and all of these birds passed viable T. ocellata eggs by day 20 indicating that protective immunity had not been transferred. Another set was killed 3-5 days after exposure. The schistosomula which were recovered from these were measured and in most cases no difference between experimentals and controls could be seen. However, birds which had received the maximum dose of serum (8 ml.) did produce worms of different length, the immune serum recipients having shorter parasites than controls. A second experiment was performed in which up to 60 ml. of immune serum was injected, controls being recipients of normal serum or saline. Recipients of immune serum either failed to pass worm eggs entirely, or passed low numbers after delayed onset. Controls were variable but exhibited earlier patency and heavier infections. Schistosomula recovered from birds killed 4 days after exposure were measured. In 3 of 4 groups, experimentals were significantly shorter than controls, but no significant differences were detected between normal serum and saline controls.