Variation analysis of transcriptome changes reveals cochlear genes and their associated functions in cochlear susceptibility to acoustic overstimulation.

Individual variation in the susceptibility of the auditory system to acoustic overstimulation has been well-documented at both the functional and structural levels. However, the molecular mechanism responsible for this variation is unclear. The current investigation was designed to examine the variation patterns of cochlear gene expression using RNA-seq data and to identify the genes with expression variation that increased following acoustic trauma. This study revealed that the constitutive expressions of cochlear genes displayed diverse levels of gene-specific variation. These variation patterns were altered by acoustic trauma; approximately one-third of the examined genes displayed marked increases in their expression variation. Bioinformatics analyses revealed that the genes that exhibited increased variation were functionally related to cell death, biomolecule metabolism, and membrane function. In contrast, the stable genes were primarily related to basic cellular processes, including protein and macromolecular syntheses and transport. There was no functional overlap between the stable and variable genes. Importantly, we demonstrated that glutamate metabolism is related to the variation in the functional response of the cochlea to acoustic overstimulation. Taken together, the results indicate that our analyses of the individual variations in transcriptome changes of cochlear genes provide important information for the identification of genes that potentially contribute to the generation of individual variation in cochlear responses to acoustic overstimulation.

Molecular profile of cochlear immunity in the resident cells of the organ of Corti.

BACKGROUND: The cochlea is the sensory organ of hearing. In the cochlea, the organ of Corti houses sensory cells that are susceptible to pathological insults. While the organ of Corti lacks immune cells, it does have the capacity for immune activity. We hypothesized that resident cells in the organ of Corti were responsible for the stress-induced immune response of the organ of Corti. This study profiled the molecular composition of the immune system in the organ of Corti and examined the immune response of non-immune epithelial cells to acoustic overstimulation. METHODS: Using high-throughput RNA-sequencing and qRT-PCR arrays, we identified immune- and inflammation-related genes in both the cochlear sensory epithelium and the organ of Corti. Using bioinformatics analyses, we cataloged the immune genes expressed. We then examined the response of these genes to acoustic overstimulation and determined how changes in immune gene expression were related to sensory cell damage. RESULTS: The RNA-sequencing analysis reveals robust expression of immune-related genes in the cochlear sensory epithelium. The qRT-PCR array analysis confirms that many of these genes are constitutively expressed in the resident cells of the organ of Corti. Bioinformatics analyses reveal that the genes expressed are linked to the Toll-like receptor signaling pathway. We demonstrate that expression of Toll-like receptor signaling genes is predominantly from the supporting cells in the organ of Corti cells. Importantly, our data demonstrate that these Toll-like receptor pathway genes are able to respond to acoustic trauma and that their expression changes are associated with sensory cell damage. CONCLUSION: The cochlear resident cells in the organ of Corti have immune capacity and participate in the cochlear immune response to acoustic overstimulation.

Spontaneous rupture of the gall bladder: an unusual forensic diagnosis.

Peritonitis secondary to spontaneous rupture/perforation of the gall bladder is a rare condition overall and is even less common in the forensic population. We report the case of a middle-aged man who died from generalized peritonitis from gall bladder perforation due to acute acalculous cholecystitis. This condition usually occurs in critical patients with systemic illness, and although the exact pathogenesis remains unclear, the development of acalculous cholecystitis appears to be multifactorial. Antemortem diagnosis is reliant upon clinical presentation, laboratory data, and radiologic studies. Surgery and appropriate antibiotics are mainstays of treatment; however, there is an emerging role for minimally invasive procedures. Histopathologic features show significant overlap with the calculous type. Although increasing numbers of acalculous cholecystitis have been diagnosed in the critically ill, the fatal presentation of a perforated gall bladder following an undiagnosed case of acute acalculous cholecystitis is unusual in a nonhospitalized and ambulatory man.

Metalloproteinases and their associated genes contribute to the functional integrity and noise-induced damage in the cochlear sensory epithelium.

Matrix metalloproteinases (MMPs) and their related gene products regulate essential cellular functions. An imbalance in MMPs has been implicated in various neurological disorders, including traumatic injuries. Here, we report a role for MMPs and their related gene products in the modulation of cochlear responses to acoustic trauma in rats. The normal cochlea was shown to be enriched in MMP enzymatic activity, and this activity was reduced in a time-dependent manner after traumatic noise injury. The analysis of gene expression by RNA sequencing and qRT-PCR revealed the differential expression of MMPs and their related genes between functionally specialized regions of the sensory epithelium. The expression of these genes was dynamically regulated between the acute and chronic phases of noise-induced hearing loss. Moreover, noise-induced expression changes in two endogenous MMP inhibitors, Timp1 and Timp2, in sensory cells were dependent on the stage of nuclear condensation, suggesting a specific role for MMP activity in sensory cell apoptosis. A short-term application of doxycycline, a broad-spectrum inhibitor of MMPs, before noise exposure reduced noise-induced hearing loss and sensory cell death. In contrast, a 7 d treatment compromised hearing sensitivity and potentiated noise-induced hearing loss. This detrimental effect of the long-term inhibition of MMPs on noise-induced hearing loss was further confirmed using targeted Mmp7 knock-out mice. Together, these observations suggest that MMPs and their related genes participate in the regulation of cochlear responses to acoustic overstimulation and that the modulation of MMP activity can serve as a novel therapeutic target for the reduction of noise-induced cochlear damage.

Applying analytical ultracentrifugation to nanocrystal suspensions.

While applied frequently in physical biochemistry to the study of protein complexes, the quantitative use of analytical ultracentrifugation (AUC) for nanocrystal analysis is relatively rare. Its application in nanoscience is potentially very powerful as it provides a measure of nanocrystal density, size and structure directly in the solution phase. Towards that end, this paper examines the best practices for applying data collection and analysis methods for AUC, geared towards the study of biomolecules, to the unique problems of nanoparticle analysis. Using uniform nanocrystals of cadmium selenide, we compared several schemes for analyzing raw sedimentation data. Comparable values of the mean sedimentation coefficients (s-value) were found using several popular analytical approaches; however, the distribution in sample s-values is best captured using the van Holde-Weischt algorithm. Measured s-values could be reproducibly collected if sample temperature and concentration were controlled; under these circumstances, the variability for average sedimentation values was typically 5%. The full shape of the distribution in s-values, however, is not easily subjected to quantitative interpretation. Moreover, the selection of the appropriate sedimentation speed is crucial for AUC of nanocrystals as the density of inorganic nanocrystals is much larger than that of solvents. Quantitative analysis of sedimentation properties will allow for better agreement between experimental and theoretical models of nanocrystal solution behavior, as well as providing deeper insight into the hydrodynamic size and solution properties of nanomaterials.

Comparative genome sequence analysis of multidrug-resistant Acinetobacter baumannii.

The recent emergence of multidrug resistance (MDR) in Acinetobacter baumannii has raised concern in health care settings worldwide. In order to understand the repertoire of resistance determinants and their organization and origins, we compared the genome sequences of three MDR and three drug-susceptible A. baumannii isolates. The entire MDR phenotype can be explained by the acquisition of discrete resistance determinants distributed throughout the genome. A comparison of closely related MDR and drug-susceptible isolates suggests that drug efflux may be a less significant contributor to resistance to certain classes of antibiotics than inactivation enzymes are. A resistance island with a variable composition of resistance determinants interspersed with transposons, integrons, and other mobile genetic elements is a significant but not universal contributor to the MDR phenotype. Four hundred seventy-five genes are shared among all six clinical isolates but absent from the related environmental species Acinetobacter baylyi ADP1. These genes are enriched for transcription factors and transporters and suggest physiological features of A. baumannii that are related to adaptation for growth in association with humans.

Size-dependent sedimentation properties of nanocrystals.

Centrifugation is an increasingly important technique for nanomaterial processing. Here, we examine this process for gold, cadmium selenide, and iron oxide nanocrystals using an analytical ultracentrifuge. Such data provide an accurate measure of the sedimentation coefficients for these materials, and we find that this parameter has a significant dependence on the size and surface coating. Conventional models for particle sedimentation cannot capture the behavior of these nanocrystals unless the density of the nanocrystals is described by a size-dependent term that accounts for both the inorganic core and the organic coating. Using this modification in the particle sedimentation framework, it is possible to estimate sedimentation coefficients from information about the nanocrystal core and surface coating dimensions. Such data are useful in choosing the speeds for a centrifugation process and are particularly important when bimodal nanocrystal distributions are present.

Chiropractic management of cow's milk protein intolerance in infants with sleep dysfunction syndrome: a therapeutic trial.

OBJECTIVE: In addition to the more usual cutaneous, gastrointestinal, and respiratory problems, infants with cow's milk intolerance (CMI) may present with a disturbed sleep pattern. Frustrated mothers may turn to their doctor of chiropractic for assistance. This pilot study shows how a therapeutic trial may offer a realistic, noninvasive approach to the chiropractic management of infants with this clinical problem. METHODS: A pilot study to describe the presentation and treatment of infants presenting with disturbed sleep patterns to a chiropractic clinic was undertaken. Infants fulfilling a clinical screening protocol for CMI were selected for a therapeutic trial. The sleep behavior of subjects was monitored over a 4-week period during which they were managed by dietary change and a high-impulse, low-amplitude whole-of-body chiropractic management protocol. RESULTS: Fifty-nine infants presented with disturbed sleep. Of these, 19 met the clinical criteria used to establish the diagnosis CMI. The mothers of breast-fed infants were counseled on how to implement a dairy-free diet, and those infants who were artificially fed were changed from cow's milk-based formulae to either a partially or wholly hydrolyzed formula. Fourteen achieved a stable sleep pattern within the study period. In 5 instances, the sleep pattern remained problematic, but other clinical evidence of hypersensitivity reactions attributable to CMI disappeared. By the end of the study, no subject had demonstrable evidence of either biomechanical derangement or functional neurologic imbalance. CONCLUSION: CMI should be considered as a possibility in infants with disturbed sleep patterns who present for chiropractic care. This study describes how a therapeutic trial involving dietary modification, parental counseling, and comprehensive chiropractic care may offer a noninvasive approach to excluding and/or managing this condition. Further research is required before definitive recommendations can be made.

Teaching diagnostic decision making: student evaluation of a diagnosis unit.

OBJECTIVE: The aim of the study was to report on chiropractic students' response to a changed learning format and on how the students fared in their final examination. METHODS: A 13-week year-4 diagnosis unit that used a structured self-study guide, a prescribed text, classroom clinical simulations, WebCT-based learning, and self-assessment tasks is described. After 4 weeks of study, a questionnaire was used to assess the chiropractic students' interim evaluation of the various learning experiences. The ability of students to meet unit objectives was assessed in a summative examination. RESULTS: Most students found the learning experiences acceptable and believed the learning options provided would enable them to meet the unit aims. This belief was confirmed both on formative and summative student assessment. CONCLUSION: Diverse classroom teaching/learning opportunities combined with self-learning guides provide a viable alternative to more traditional teaching formats for introducing chiropractic students to differential diagnosis.

Low back pain risk factors in a large rural Australian Aboriginal community. An opportunity for managing co-morbidities?

BACKGROUND: Low back pain (LBP) is the most prevalent musculo-skeletal condition in rural and remote Australian Aboriginal communities. Smoking, physical inactivity and obesity are also prevalent amongst Indigenous people contributing to lifestyle diseases and concurrently to the high burden of low back pain. OBJECTIVES: This paper aims to examine the association between LBP and modifiable risk factors in a large rural Indigenous community as a basis for informing a musculo-skeletal and related health promotion program. METHODS: A community Advisory Group (CAG) comprising Elders, Aboriginal Health Workers, academics, nurses, a general practitioner and chiropractors assisted in the development of measures to assess self-reported musculo-skeletal conditions including LBP risk factors. The Kempsey survey included a community-based survey administered by Aboriginal Health Workers followed by a clinical assessment conducted by chiropractors. RESULTS: Age and gender characteristics of this Indigenous sample (n = 189) were comparable to those reported in previous Australian Bureau of Statistics (ABS) studies of the broader Indigenous population. A history of traumatic events was highly prevalent in the community, as were occupational risk factors. Thirty-four percent of participants reported a previous history of LBP. Sporting injuries were associated with multiple musculo-skeletal conditions, including LBP. Those reporting high levels of pain were often overweight or obese and obesity was associated with self-reported low back strain. Common barriers to medical management of LBP included an attitude of being able to cope with pain, poor health, and the lack of affordable and appropriate health care services. Though many of the modifiable risk factors known to be associated with LBP were highly prevalent in this study, none of these were statistically associated with LBP. CONCLUSION: Addressing particular modifiable risk factors associated with LBP such as smoking, physical inactivity and obesity may also present a wider opportunity to prevent and manage the high burden of illness imposed by co-morbidities such as heart disease and type-2 diabetes.

Fostering critical thinking skills: a strategy for enhancing evidence based wellness care.

UNLABELLED: Chiropractic has traditionally regarded itself a wellness profession. As wellness care is postulated to play a central role in the future growth of chiropractic, the development of a wellness ethos acceptable within conventional health care is desirable. This paper describes a unit which prepares chiropractic students for the role of "wellness coaches". Emphasis is placed on providing students with exercises in critical thinking in an effort to prepare them for the challenge of interfacing with an increasingly evidence based health care system. METHODS: This case study describes how health may be promoted and disease prevented through development of personalized wellness programs. As critical thinking is essential to the provision of evidence based wellness care, diverse learning opportunities for developing and refining critical thinking skills have been created. Three of the learning opportunities are an intrinsic component of the subject and, taken together, contributed over 50% of the final grade of the unit. They include a literature review, developing a client wellness contract and peer evaluation. In addition to these 3 compulsory exercises, students were also given an opportunity to develop their critical appraisal skills by undertaking voluntary self- and unit evaluation. Several opportunities for informal self-appraisal were offered in a structured self-study guide, while unit appraisal was undertaken by means of a questionnaire and group discussion at which the Head of School was present. RESULTS: Formal assessment showed all students capable of preparing a wellness program consistent with current thinking in contemporary health care. The small group of students who appraised the unit seemed to value the diversity of learning experiences provided. Opportunities for voluntary unit and self-appraisal were used to varying degrees. Unit evaluation provided useful feedback that led to substantial changes in unit structure. CONCLUSION: Students have demonstrated themselves capable of applying critical thinking in construction of evidence based wellness programs. With respect to unit design, selective use of learning opportunities highlighted the desirability of using obligatory learning opportunities to ensure exposure to core constructs while student feedback was found to provide useful information for enriching unit review. It is hoped inclusion of critical thinking learning opportunities in the undergraduate chiropractic curriculum will contribute to the development of an evidence based ethos in chiropractic care.

Analytical ultracentrifugation for characterizing nanocrystals and their bioconjugates.

Analytical ultracentrifugation (AU) provides a general way to probe the polydispersity of nanoparticles and the formation of bioconjugates in solution. Unconjugated gold nanocrystals show sedimentation coefficient distributions that are in agreement with size distributions as measured by TEM. AU is sensitive to the size/shape changes elicited by conjugation, in this case to lactose repressor (LacI). AU data reveal saturating protein concentrations for conjugates that correspond to the measured stoichiometry of the complex under these conditions.

Insomnia: does chiropractic help?

OBJECTIVE: To evaluate the effect of chiropractic care on insomnia. DESIGN: Tripartite pilot study. METHODS: The expectations of the chiropractic community were canvassed, a retrospective study to recall changes in sleep patterns was undertaken, and a prospective pilot study to monitor sleep patterns after chiropractic care was carried out. Convenience sampling was used. RESULTS: The 221 patients and 15 chiropractors who completed the expectation study tended to believe that patients with sleeping difficulties benefited from chiropractic care. The chiropractors were more guarded in their expectations than participating patients. One third of the 154 patients who completed the semistructured interview reported their sleep pattern was changed immediately after their chiropractic adjustment. All but 1 of these 52 patients reported improvement. Twenty patients with insomnia participated in the prospective study. Although compared with the report in their screening questionnaire, improvement was noted in certain sleep parameters in the 6 days after their adjustment, no temporal trends emerged in the days and/or weeks after the chiropractic consultation. Most patients reported experiencing less or no discomfort during the duration of the study. CONCLUSION: Although a number of patients do perceive chiropractic care offers temporary respite from their insomnia problem, when changes were more objectively monitored, improvements were erratic and no consistent temporal trends were detectable. Convincing evidence has yet to be produced before routine chiropractic care can be considered adequate intervention for patients with sleeping difficulties. More definitive answers may result from future research being undertaken in sleep laboratories.

Prescribing wellness: a case study exploring the use of health information brochures.

OBJECTIVE: A case study was undertaken to ascertain the potential usefulness of brochures as a strategy for encouraging short-term and longer-term acquisition of healthy behaviors at the consumer-health care system interface. METHOD: Purposive sampling of chiropractic clinics and convenience sampling of patients attending these primary contact practitioners were undertaken. Patients were asked to complete a questionnaire. Interested patients were given a health information brochure on topics of their choice. Patients who had requested health information brochures were phoned at 3 weeks, 3 months, and 1 year after completing the initial questionnaire and asked if they had implemented any of the suggestions for health promotion or risk prevention. A minimum of 4 attempts were made to contact each participant by telephone. Data were analyzed using descriptive statistics. RESULTS: Twenty-one chiropractic clinics and 781 patients participated. Although every third patient requested one or more health information brochures, fewer than 1 in 4 of those receiving brochures implemented some health-promoting behavior. Although some patients persisted with their newly initiated health-promoting behaviors, compliance diminished over time. Exercise and dietary change were the behaviors most likely to be modified. CONCLUSION: Implementation of even one healthy behavior can have a ubiquitous health benefit. Despite dwindling compliance, it is therefore suggested that suitably formulated health information brochures that inform and encourage adoption of healthy behaviors by motivated patients deserve consideration by all health professionals working at the consumer-health care system interface.

Dietary diversity: case study of fruit and vegetable consumption by chiropractic patients.

BACKGROUND: A distinct health advantage has been linked with eating a wide variety of fresh fruit and vegetables. OBJECTIVE: This study explores the diversity of fruits and vegetables consumed by chiropractic patients and inquires into their preferred purchasing patterns. METHOD: A case study that included patients attending 24 chiropractic practices in 5 states and the Australian Capital Territory was undertaken. Seven hundred eighty-two patients were asked to complete a questionnaire providing general information about their life-style and particular information about the number of servings of fruits and vegetables that they usually consumed. RESULTS: Although overall chiropractic patients reported adhering to a number of healthy life-style behaviors, participants in this study would benefit from eating a greater diversity of fruits and vegetables. CONCLUSION: In view of the substantial health benefits associated with eating a wide variety of fruits and vegetables, it is suggested that chiropractic patients be encouraged to follow a color code system for purchasing their fresh produce.

Herbal and nutrient supplementation practices of chiropractic patients: an Australian case study.

BACKGROUND: Escalating interest in alternative health care has resulted in increased use of nutritional supplements and herbs by consumers. A number of these neutraceuticals interact with prescription drugs and may have adverse effects. OBJECTIVE: This study explored the extent to which chiropractic patients are likely to inform their chiropractic practitioner of their medication practices. METHOD: A case study that included patients attending 21 chiropractic clinics in 5 states and the Australian Capital Territory was undertaken. Seven hundred fifty-eight patients provided information on their nutritional and herbal supplementation practices. Data were collected using a questionnaire that inquired about general life-style and sought particular information about self-initiated and professionally recommended medication practices. A list of medications that could influence coagulation was provided. Patients were specifically requested to indicate whether they had informed their chiropractor about any of the medications, herbs, or nutrients they were taking. RESULTS: More than 1 in 3 of the chiropractic patients in this study were taking, either on the advice of a health professional or, more often, on their own initiative, a nutritional supplement and/or herb. Yet, chiropractors were only occasionally informed about the medication practices of their patients. CONCLUSION: In view of the potential health risks and drug interactions, chiropractors should routinely inquire whether their patients are taking herbs or nutritional supplements.

Health information and promotion in chiropractic clinics.

OBJECTIVE: To explore the current health education behaviors of chiropractors, ascertain their willingness to provide patient counseling, and compare this with topics of interest to chiropractic patients. METHODS: This study involved a postal survey of 400 randomly selected members of the Chiropractic Association of Australia (35% response rate) and a semistructured interview of 316 patients attending one of 20 purposively selected chiropractic practices. Data were collated, and the current health information practices of chiropractic respondents and their willingness to undertake counseling on various topics was identified and compared with the information interests of participating patients. Particular emphasis was placed on injury prevention both with respect to patient counseling and chiropractic practice risk. RESULTS: Respondents expressed varying degrees of willingness to provide health information on diverse topics, but no clear health education chiropractic practice pattern emerged. Although expressing willingness to undertake counseling, respondents were more likely to provide health information brochures than develop a tailored health promotion contract. Health education topics ranged from exercise (91%) to osteoporosis prevention (23%). Seventy-eight percent of chiropractors were prepared to offer counseling on injury prevention, yet 45% of respondents themselves reported having some work-related injury. Maintenance care failed to emerge as a global term for describing a common core of topics or chiropractic health education practices. CONCLUSION: This study demonstrated an interest by chiropractors in providing and by chiropractic patients in obtaining health information that extends beyond spinal health. The range of relevant topics covered and modes used for health information transmission in chiropractic practice requires clarification. The prevalence of work-related injury among chiropractors suggests a need to develop safe chiropractic clinical practice protocols.

Self-care: An Australian case study of chiropractic patients.

OBJECTIVE: Self-care is becoming an important objective for achieving a sustainable health care system. This study examines the health care initiatives of chiropractic patients ascertaining their self-care behaviors, knowledge and information sources. SAMPLE: Convenience sampling of chiropractic patients attending 10 chiropractors in 3 states. Of 155 patients invited to participate, 147 agreed. METHOD: Patients were interviewed to determine their smoking, alcohol, maintenance chiropractic care, exercise and nutritional supplementation practices. Data collection included dose/frequency of the activity, expected benefits, concerns about side-effects and sources of information. Data was collated and trends identified. RESULTS: Overall, the chiropractic patient sample reported a healthy lifestyle. Seventy-four percent (74%) had maintenance chiropractic; 69%, regular exercise; 40%, nutritional supplements; 84%, were non-smokers; and 86% were teetotallers or drank alcohol within safe limits. Few displayed appreciation of possible side-effects or 'dose-response' relationships. Lay persons were important information sources. CONCLUSION: Chiropractic patients' self-care behaviors could be refined by making them more aware of the protean effects of self-care initiatives.

A psychological profile of chiropractic patients: an australian case study.

BACKGROUND: The efficiency and efficacy of the chiropractic consultation would be enhanced if patients requiring additional psychological assistance could be identified. Distressed patients and those with a low sense of coherence and/or manageability score may benefit from a more prolonged chiropractic consultation or may require specialist referral. OBJECTIVE: This exploratory study sought to ascertain whether categorization within a particular chiropractic management group could serve as a red flag to alert the practitioner to the likelihood of special patient needs. RESEARCH METHOD: A case study to explore the psychological profile of chiropractic patients was undertaken. The DRAM (Distress and Risk Assessment Method) and SOC (Sense of Coherence) questionnaires were used to ascertain the distress and sense of coherence and manageability levels of acute, chronic and maintenance chiropractic patients. Purposive sampling of practitioners and convenience sampling of patients fulfilling the study's inclusion criteria was undertaken. Patients were requested to complete two and chiropractors to complete one questionnaire and an interview. RESULTS: Ten chiropractors and 142 patients participated in the study. Of participating patients, 38% had a chronic biomechanical problem, 23% were acute, and 39% were maintenance patients. Acute, chronic and maintenance patients were spread along the entire spectrum of the SOC and manageability scale. Of the 130 patients who completed the DRAM section of the questionnaire, over one in five were distressed. CONCLUSION: Due to the small sample size and the diversity of results it was not possible to identify particular groups of chiropractic patients who require additional consultation time or referral. This study did however demonstrate that some chiropractic patients are distressed and consequently it is important that chiropractors know when to manage and when to refer anxious or depressed patients.