Characterization of the Sheep Round Window Membrane.

Intratympanic injection is a clinically used approach to locally deliver therapeutic molecules to the inner ear. Drug diffusion, at least in part, is presumed to occur through the round window membrane (RWM), one of the two openings to the inner ear. Previous studies in human temporal bones have identified a three-layered structure of the RWM with a thickness of 70-100 µm. This is considerably thicker than the RWM in rodents, which are mostly used to model RWM permeability and assess drug uptake. The sheep has been suggested as a large animal model for inner ear research given the similarities in structure and frequency range for hearing. Here, we report the structure of the sheep RWM. The RWM is anchored within the round window niche (average vertical diameter of 2.1 ± 0.3 mm and horizontal diameter of 2.3 ± 0.4 mm) and has a curvature that leans towards the scala tympani. The centre of the RWM is the thinnest (55-71 µm), with increasing thickness towards the edges (< 171 µm), where the RWM forms tight attachments to the surrounding bony niche. The layered RWM structure, including an outer epithelial layer, middle connective tissue and inner epithelial layer, was identified with cellular features such as wavy fibre bundles, melanocytes and blood vessels. An attached "meshwork structure" which extends over the cochlear aqueduct was seen, as in humans. The striking anatomical similarities between sheep and human RWM suggest that sheep may be evaluated as a more appropriate system to predict RWM permeability and drug delivery in humans than rodent models.

Review: Role of herbivores in sustainable agriculture in Sub-Saharan Africa.

The role of herbivorous livestock in supporting the sustainability of the farming systems in which they are found is complex and sometimes conflicting. In Sub-Saharan Africa (SSA), the integration of livestock into farming systems is important for sustainable agriculture as the recycling of nutrients for crop production through returns of animal manure is a central element of the dominant mixed crop-livestock systems. Sustainable agriculture has been widely advocated as the main practical pathway to address the challenge of meeting the food needs of the rapidly growing population in SSA while safeguarding the needs of future generations. The objective of this paper is to review the state of knowledge of the role of herbivores in sustainable intensification of key farming systems in SSA. The pathways to sustainable agriculture in SSA include intensification of production and livelihood diversification. Sustainable agricultural practices in SSA have focused on intensification practices which aim to increase the output : input ratio through increasing use of inputs, introduction of new inputs or use of existing inputs in a new way. Intensification of livestock production can occur through increased and improved fodder availability, genetic production gains, improved crop residue use and better nutrient recycling of manure. Livestock deliver many 'goods' in smallholder farming systems in SSA including improving food and nutrition security, increased recycling of organic matter and nutrients and the associated soil fertility amendments, adding value to crop residues by turning them into nutrient-rich foods, income generation and animal traction. Narratives on livestock 'bads' or negative environmental consequences have been largely shaped by the production conditions in the Global North but livestock production in SSA is a different story. In SSA, livestock are an integral component of mixed farming systems and they play key roles in supporting the livelihoods of much of the rural population. None-the-less, the environmental consequences of livestock production on the continent cannot be ignored. To enhance agricultural sustainability in SSA, the challenge is to optimize livestock's role in the farming systems by maximizing livestock 'goods' while minimizing the 'bads'. This can be through better integration of livestock into the farming systems, efficient nutrient management systems, and provision of necessary policy and institutional support.

Tagasaste (Chamaecytisus palmensis) leaf supplementation to enhance nutrient intake and production performance of sheep in the Ethiopian highlands.

The objective of this study was to determine the effect of supplementing increasing levels of dried tagasaste (Chamaecytisus palmensis) leaf on the nutrition and performance of sheep fed a basal diet of barley straw. The study had four treatments, which involved supplementation of dried tagasaste leaf at 100, 200, 300, and 400 g/day. Twenty-four yearling Menz sheep (weight 17 ± 0.83 kg) were assigned to one of the four treatments in a randomized complete block design. The experiment comprised a feeding trial lasting for 90 days, a digestibility trial, and carcass evaluation using all animals. Samples of the feed consumed, refused, and feces were analyzed for nutrients. Intake and digestibility of dry matter (DM) and nutrients increased linearly (P < 0.001) as tagasaste supplementation increased from 100 to 400 g/day. Similarly, average daily body weight gain increased linearly (P < 0.001) from 20 to 73 g/day, feed conversion efficiency from 0.04 to 0.10, and dressing percentage from 40 to 48%, as the supplementation increased from 100 to 400 g/day. Proportion of tagasaste leaf in the diet increased from 20 to 50%, while the ratio of neutral detergent fiber (NDF) to crude protein (CP) decreased from 7.9 to 5.3, as the level of supplementation increased. It was thus concluded that supplementation of dried tagasaste leaf up to 50% of the diet DM, resulting in a NDF:CP ratio of 5.3, produces no deleterious effects on the performance of sheep, and inclusion to this level can be applied for superior growth performance and carcass yield in sheep fed crop residue-based diets.

Reduced sensory stimulation alters the molecular make-up of glutamatergic hair cell synapses in the developing cochlea.

Neural activity during early development is known to alter innervation pathways in the central and peripheral nervous systems. We sought to examine how reduced sound-induced sensory activity in the cochlea affected the consolidation of glutamatergic synapses between inner hair cells (IHC) and the primary auditory neurons as these synapses play a primary role in transmitting sound information to the brain. A unilateral conductive hearing loss was induced prior to the onset of sound-mediated stimulation of the sensory hair cells, by rupturing the tympanic membrane and dislocating the auditory ossicles in the left ear of P11 mice. Auditory brainstem responses at P15 and P21 showed a 40-50-dB increase in thresholds for frequencies 8-32kHz in the dislocated ear relative to the control ear. Immunohistochemistry and confocal microscopy were subsequently used to examine the effect of this attenuation of sound stimulation on the expression of RIBEYE, which comprises the presynaptic ribbons, Shank-1, a postsynaptic scaffolding protein, and the GluA2/3 and 4 subunits of postsynaptic AMPA receptors. Our results show that dislocation did not alter the number of pre- or postsynaptic protein puncta. However, dislocation did increase the size of RIBEYE, GluA4, GluA2/3 and Shank-1 puncta, with postsynaptic changes preceding presynaptic changes. Our data suggest that a reduction in sound stimulation during auditory development induces plasticity in the molecular make-up of IHC glutamatergic synapses, but does not affect the number of these synapses. Up-regulation of synaptic proteins with sound attenuation may facilitate a compensatory increase in synaptic transmission due to the reduced sensory stimulation of the IHC.

Electrostatic dust collectors compared to inhalable samplers for measuring endotoxin concentrations in farm homes.

Paired electrostatic dust collectors (EDCs) and daily, inhalable button samplers (BS) were used concurrently to sample endotoxin in 10 farm homes during 7-day periods in summer and winter. Winter sampling included an optical particle counter (OPC) to measure PM2.5 and PM2.5-10 . Electrostatic dust collectors and BS filters were analyzed for endotoxin using the kinetic chromogenic Limulus amebocyte lysate assay. Optical particle counter particulate matter (PM) data were divided into two PM categories. In summer, geometric mean (geometric standard deviation) endotoxin concentrations were 0.82 EU/m(3) (2.7) measured with the BS and 737 EU/m(2) (1.9) measured with the EDC. Winter values were 0.52 EU/m(3) (3.1) for BS and 538 EU/m(2) (3.0) for EDCs. Seven-day endotoxin values of EDCs were highly correlated with the 7-day BS sampling averages (r = 0.70; P < 0.001). Analysis of variance indicated a 2.4-fold increase in EDC endotoxin concentrations for each unit increase of the ratio of PM2.5 to PM2.5-10 . There was also a significant correlation between BS and EDCs endotoxin concentrations for winter (r = 0.67; P < 0.05) and summer (r = 0.75; P < 0.05). Thus, EDCs sample comparable endotoxin concentrations to BS, making EDCs a feasible, easy to use alternative to BS for endotoxin sampling.

High frequency bone conduction auditory evoked potentials in the guinea pig: Assessing cochlear injury after ossicular chain manipulation.

Permanent high frequency (>4 kHz) sensorineural hearing loss following middle ear surgery occurs in up to 25% of patients. The aetiology of this loss is poorly understood and may involve transmission of supra-physiological forces down the ossicular chain to the cochlea. Investigating the mechanisms of this injury using animal models is challenging, as evaluating cochlear function with evoked potentials is confounded when ossicular manipulation disrupts the normal air conduction (AC) pathway. Bone conduction (BC) using clinical bone vibrators in small animals is limited by poor transducer output at high frequencies sensitive to trauma. The objectives of the present study were firstly to evaluate a novel high frequency bone conduction transducer with evoked auditory potentials in a guinea pig model, and secondly to use this model to investigate the impact of middle ear surgical manipulation on cochlear function. We modified a magnetostrictive device as a high frequency BC transducer and evaluated its performance by comparison with a calibrated AC transducer at frequencies up to 32 kHz using the auditory brainstem response (ABR), compound action potential (CAP) and summating potential (SP). To mimic a middle ear traumatising stimulus, a rotating bur was brought in to contact with the incudomalleal complex and the effect on evoked cochlear potentials was observed. BC-evoked potentials followed the same input-output function pattern as AC potentials for all ABR frequencies. Deterioration in CAP and SP thresholds was observed after ossicular manipulation. It is possible to use high frequency BC to evoke responses from the injury sensitive basal region of the cochlea and so not rely on AC with the potential confounder of conductive hearing loss. Ongoing research explores how these findings evolve over time, and ways in which injury may be reduced and the cochlea protected during middle ear surgery.

Development of the hearing protection assessment (HPA-2) questionnaire.

BACKGROUND: Noise-induced hearing loss (NIHL) remains an important occupational health issue as the second most commonly self-reported occupational injury or illness. The incorrect and inconsistent use of hearing protection devices (HPDs) compromises their effectiveness in preventing NIHL. AIMS: To describe the development of an easily administered yet robust questionnaire to investigate factors that influence HPD use. METHODS: A hearing protection assessment (HPA-2) questionnaire was developed using items based on themes identified in our previous research. These fell into two classes: supports and barriers to wearing HPD, which formed two scales within the questionnaire. The questionnaire, which also included demographic items, was administered to workers from 34 manufacturing companies. The internal consistency of the scales was tested, and factor analysis was conducted to investigate the underlying structure of the scales. RESULTS: Of the 1053 questionnaires distributed, 555 completed questionnaires were received giving a response rate of 53%. The Cronbach's alpha for the barriers scale (α = 0.740) and supports scale (α = 0.771) indicated strong internal reliability of the questionnaire. The supports and barriers were further described as five key factors (risk justification, HPD constraints, hazard recognition, behaviour motivation and safety culture) that influence hearing protection behaviour. Workers who reported always using HPDs had more supports across these factors, while those who did not always wear HPDs reported more barriers. CONCLUSIONS: The HPA-2 questionnaire may be useful in both research and interventions to understand and motivate hearing protection behaviour by identifying and targeting supports and barriers to HPD use at different levels of the ecological model.

Noise exposure of workers and the use of hearing protection equipment in New Zealand.

Hearing loss from occupational noise exposure is a significant occupational health problem, requiring effective health and safety strategies. Essential to this is an understanding of the noise exposure of workers and the use of hearing protection equipment (HPE). This study reports on data collected in New Zealand. Visits were made to companies in each economic sector. Personal dosimetry was used to assess individual noise exposure of 529 workers. Workers were also interviewed about their use of HPE. Overall, 40.4% of production workers had a daily noise exposure greater than 1 Pa(2)h, exceeding the New Zealand National Standard for occupational noise exposure without HPE. Of these, 88.5% reported to use HPE when working in noise; however, some observations suggested that workers do not consistently use the devices. These data add to the overall picture of noise exposure of workers in New Zealand and are especially useful in areas where data did not previously exist or were difficult to access.

Residential culturable fungi, (1-3, 1-6)-ß-d-glucan, and ergosterol concentrations in dust are not associated with asthma, rhinitis, or eczema diagnoses in children.

Qualitative reporting of home indoor moisture problems predicts respiratory diseases. However, causal agents underlying such qualitative markers remain unknown. In the homes of 198 multiple allergic case children and 202 controls in Sweden, we cultivated culturable fungi by directly plating dust, and quantified (1-3, 1-6)-ß-D-glucan and ergosterol in dust samples from the child's bedroom. We examined the relationship between these fungal agents and degree of parent or inspector-reported home indoor dampness, and microbiological laboratory's mold index. We also compared the concentrations of these agents between multiple allergic cases and healthy controls, as well as IgE-sensitization among cases. The concentrations of culturable fungal agents were comparable between houses with parent and inspector-reported mold issues and those without. There were no differences in concentrations of the individual or the total summed culturable fungi, (1-3, 1-6)-ß-D-glucan, and ergosterol between the controls and the multiple allergic case children, or individual diagnosis of asthma, rhinitis, or eczema. Culturable fungi, (1-3, 1-6)-ß-D-glucan, and ergosterol in dust were not associated with qualitative markers of indoor dampness or mold or indoor humidity. Furthermore, these agents in dust samples were not associated with any health outcomes in the children.

Assessment of airborne exposures and health in flooded homes undergoing renovation.

UNLABELLED: In June 2008, the Cedar River crested flooding more than 5000 Cedar Rapids homes. Residents whose homes were flooded were invited to participate in this study. Household assessments and resident interviews were conducted between November 2008 and April 2009. We characterized exposures and symptoms experienced by individuals inhabiting 73 flood-damaged homes. Active air sampling and passive electrostatic dust collectors were used to assess exposures to culturable mold, culturable bacteria, fungal spores, inhalable particulate matter (iPM), endotoxin, glucans, allergens, lead, asbestos, radon, carbon dioxide, and carbon monoxide. Wall moisture levels and relative humidity were also measured. Exposures and questionnaire-based health assessments were compared at two levels of remediation, in-progress and completed. Homes with remediation in-progress (N = 24), as compared to the completed homes (N = 49), had significantly higher airborne concentrations of mold, bacteria, iPM, endotoxin, and glucan. Residents of in-progress homes had a significantly higher prevalence of doctor-diagnosed allergies (adjusted OR = 3.08; 95% CI: 1.05, 9.02) and all residents had elevated prevalence of self-reported wheeze (adjusted OR = 3.77; 95% CI: 2.06, 6.92) and prescription medication use for breathing problems (adjusted OR = 1.38; 95% CI: 1.01, 1.88) after the flood as compared to before. Proper post-flood remediation led to improved air quality and lower exposures among residents living in flooded homes. PRACTICAL IMPLICATIONS: The number and severity of floods is on the rise, and health departments need evidence-based information to advise homeowners on recovery after such disasters. Our study suggests that proper remediation of flood-damaged homes can reduce bioaerosols to acceptable levels but exposures are significantly increased while remediation is in-progress leading to an increased burden of allergy and allergic rhinitis.

Contribution of solid fuel, gas combustion, or tobacco smoke to indoor air pollutant concentrations in Irish and Scottish homes.

UNLABELLED: There are limited data describing pollutant levels inside homes that burn solid fuel within developed country settings with most studies describing test conditions or the effect of interventions. This study recruited homes in Ireland and Scotland where open combustion processes take place. Open combustion was classified as coal, peat, or wood fuel burning, use of a gas cooker or stove, or where there is at least one resident smoker. Twenty-four-hour data on airborne concentrations of particulate matter<2.5 µm in size (PM2.5), carbon monoxide (CO), endotoxin in inhalable dust and carbon dioxide (CO2), together with 2-3 week averaged concentrations of nitrogen dioxide (NO2) were collected in 100 houses during the winter and spring of 2009-2010. The geometric mean of the 24-h time-weighted-average (TWA) PM2.5 concentration was highest in homes with resident smokers (99 µg/m3--much higher than the WHO 24-h guidance value of 25 µg/m3). Lower geometric mean 24-h TWA levels were found in homes that burned coal (7 µg/m3) or wood (6 µg/m3) and in homes with gas cookers (7 µg/m3). In peat-burning homes, the average 24-h PM2.5 level recorded was 11 µg/m3. Airborne endotoxin, CO, CO2, and NO2 concentrations were generally within indoor air quality guidance levels. PRACTICAL IMPLICATIONS: Little is known about indoor air quality (IAQ) in homes that burn solid or fossil-derived fuels in economically developed countries. Recent legislative changes have moved to improve IAQ at work and in enclosed public places, but there remains a real need to begin the process of quantifying the health burden that arises from indoor air pollution within domestic environments. This study demonstrates that homes in Scotland and Ireland that burn solid fuels or gas for heating and cooking have concentrations of air pollutants generally within guideline levels. Homes where combustion of cigarettes takes place have much poorer air quality.

Development of a synthetic PCB mixture resembling the average polychlorinated biphenyl profile in Chicago air.

Studies of environmental and toxic effects of polychlorinated biphenyls (PCBs) are ideally performed with PCB mixtures reflecting the composition of environmental PCB profiles to mimic actual effects and to account for complex interactions among individual PCB congeners. Unfortunately, only a few laboratory studies employing synthetic PCB mixtures have been reported, in part because of the challenges associated with the preparation of complex PCB mixtures containing many individual PCB congeners. The objective of this study was to develop a PCB mixture that resembles the average PCB profile recorded from 1996 to 2002 at a satellite station of the Integrated Atmospheric Deposition Network located at the Illinois Institute of Technology (IIT) in Chicago, Illinois, using commercial PCB mixtures. Initial simulations, using published Aroclor profiles, showed that a mixture containing 65% Aroclor 1242 and 35% Aroclor 1254 was a good approximation of the target profile. A synthetic Chicago air mixture (CAM) was prepared by mixing the respective Aroclors in this ratio, followed by GC/MS/MS analysis. Comparison of the PCB profile of the synthetic mixture with the target profile suggests that the synthetic PCB mixture is a good approximation of the average IIT Chicago air profiles (similarity coefficient cos θ = 0.82; average relative percent difference = 84%). The synthetic CAM was also a reasonable approximation of the average of 184 PCB profiles analyzed in 2007 at 37 sites throughout Chicago as part of the University of Iowa Superfund Basic Research Program (isbrp), with a cos θ of 0.70 and an average relative percent difference of 118%. While the CAM and the two Chicago air profiles contained primarily di- to pentachlorobiphenyls, higher chlorinated congeners, including congeners with seven or eight chlorine atoms, were underrepresented in the synthetic CAM. The calculated TCDD toxic equivalency quotients of the synthetic CAM (2.7 ng/mg PCB) and the IIT Chicago air profile (1.6 ng/mg PCB) were comparable, but lower by two orders of magnitude than the isbrp Chicago air profile (865 ng/mg PCB) due to surprisingly high PCB 126 levels in Chicago air. In contrast, the calculated neurotoxic equivalency quotients of the CAM (0.33 mg/mg PCB) and the two Chicago air profiles (0.44 and 0.30 mg/mg PCB, respectively) were similar. This study demonstrates the challenges and methods of creating and characterizing synthetic, environmental mixtures of PCBs.

Early-life co-administration of cockroach allergen and endotoxin augments pulmonary and systemic responses.

BACKGROUND: Environmental exposures to cockroach allergen and endotoxin are recognized epidemiological risk factors for the early development of allergies and asthma in children. Because of this, it is important to examine the role of early-life concurrent inhalation exposures to cockroach allergen and endotoxin in the pathogenesis of allergic airways disease. OBJECTIVE: We examined the effects of repeated concomitant endotoxin and cockroach allergen inhalation on the pulmonary and systemic immune responses of newborn and juvenile mice. METHODS: C3H/HeBFeJ mice were exposed to inhaled endotoxin and cockroach allergen via intranasal instillation from day 2 to 21 after birth, and systemic and pulmonary responses were examined in serum, bronchoalveolar lavage fluid, and lung tissue. RESULTS: Cockroach allergen exposures induced pulmonary eosinophilic inflammation, total and allergen-specific IgE, IgG(1), and IgG(2a) production, and alveolar remodelling. Co-exposures with endotoxin and cockroach allergen significantly increased serum IgE and IgG(1), lung inflammation, and alveolar wall thickness, and decreased airspace volume density. Importantly, compared with exposures with individual substances, the responses to co-exposures were more than additive. CONCLUSIONS: Repeated inhalation exposures of neonatal and juvenile mice to endotoxin and cockroach allergen increased the pulmonary inflammatory and systemic immune responses in a synergistic manner and enhanced alveolar remodelling in the developing lung. These data underscore the importance of evaluating the effect of multiple, concurrent environmental exposures, and of using an experimental model that incorporates clinically relevant timing and route of exposures.

Real-time PCR quantification of Mycobacterium immunogenum in used metalworking fluids.

Rapid detection and quantification of Mycobacterium immunogenum in field samples of metalworking fluids (MWFs) is important for factory fluid surveillance programs. The applicability of the developed DNA extraction and quantitative real-time PCR (qPCR) methods to detect and quantify M. immunogenum in used MWFs was evaluated. Total DNA from these samples was extracted, and M. immunogenum measured by qPCR by comparison with a standard curve derived from plasmid vectors. PCR counts were compared with bacterial culture counts. PCR counts of M. immunogenum varied from 1.42 x 10(3) to 3.68 x 10(6) cells/mL of MWFs. Recovery of M. immunogenum by bacterial culture varied from 2.5% to 70% of qPCR count in corresponding samples. Quantitative PCR could be used to measure M. immunogenum load in MWF samples with greater sensitivity and shorter processing time than the classic bacterial culture-based approach. The proposed qPCR approach could be routinely used in real-time PCR-equipped laboratories to provide early detection of M. immunogenum and to control proliferation that probably leads to hypersensitivity pneumonitis in exposed workers.

Acute effect of glucan-spiked office dust on nasal and pulmonary inflammation in guinea pigs.

The acute effects of pure inhaled glucan on respiratory inflammation remain inconclusive and not sufficiently examined with regards to the simultaneous interaction of glucan, endotoxin (lipopolysaccharide, LPS), and house dust in airway inflammation. This study aims at determining effects of simultaneous exposure to office dust and glucan on nasal and pulmonary inflammation. This is relevant for humans with occupational exposure in waste handling and farming and buildings with mold problems. Office dust collected from Danish offices was spiked with 1% (1-3)-beta-glucan (curdlan). Guinea pig nasal cavity volume was measured by acoustic rhinometry (AR) and animals were exposed by inhalation for 4 h to curdlan-spiked dust, unspiked dust, purified air (negative controls), or LPS (positive controls). After exposure (+5 h) or the following day (+18 h), measurements were repeated by AR and followed by bronchoalveolar lavage (BAL). Total and differential cell counts, interleukin (IL)-8 in BAL fluid, and change in nasal volume were compared between groups. A 5-10% increase in nasal volume was seen for all groups including clean air except for a significant 5% decrease for spiked-dust inhalation (+18 h). No marked differences were observed in BAL cells or IL-8 except in LPS-exposed controls. The delayed decrease of nasal cavity volume after exposure to glucan spiked dust suggests a slow effect on the upper airways for curdlan and office dust together, though no pulmonary response or direct signs of inflammation were observed. Glucan-spiked office dust exposures produced a delayed nasal subacute congestion in guinea pigs compared to office dust alone, but extrapolated to nasal congestion in humans, paralleling the nasal congestion seen in human volunteers exposed to the same dust, this may not have clinical importance.