Do goblet cell mediators co-operatively prevent gut microbiota from causing spontaneous colitis?

Inflammatory Bowel Diseases, including Crohn’s disease and ulcerative colitis are characterized by chronic intestinal inflammation and tissue damage. There are trillions of bacteria found  within the human intestine and IBDs are thought to develop when mucus barriers that normally keep these  bacteria inside the gastrointestinal tract become impaired,  allowing bacteria to escape out of the gut lumen and causing  chronic inflammation. While the role of epithelial cells in promoting barrier function is well known, the protective actions of the mucus barrier are relatively understudied.

Specialized secretory epithelial cells known as goblet cells within the gut lumen produce  mucins known as Muc2 and pro-inflammatory proteins called  RELM-ß. Through in vitro and in vivo studies, and  microbiota analysis, Morampudi plans to define how these goblet cell proteins cooperatively protect the intestine from  developing spontaneous colitis through the development of  these products.Through tests with micelacking either Muc2 or RELM-ß, Dr. Morampudi has  hypothesized that both proteins act together to protect the  intestine from gut commensal bacteria. Muc2 provides a  structural barrier, preventing bacteria from contacting the immune system, but when the mucus barrier is impaired,  RELM-ß is induced to create an antimicrobial zone above the  intestinal epithelium. Under conditions where expression of  both proteins is impaired (such as by ER stress), the  commensal bacteria are able to escape from the intestine and cause colitis/IBD.Ultimately, this research will provide insights as to how  the development of spontaneous colitis can be prevented.


Gender Differences in the Diagnosis and Management of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD), has generally been thought of as a ""man's disease."" However, there has been a substantial increase in the prevalence and mortality of COPD in women recently, with a tripling of the female mortality rate over the past 20 years compared with a stable mortality rate in men over that same time period. The increased prevalence and mortality of COPD in women has been attributed to an increase in smoking rates in women, which began over 50 years ago. Recent studies have shown that women may be more susceptible to the effects of cigarette smoke compared to men. In addition, there is evidence to suggest that a gender bias may exist with respect to diagnosis; specifically, that women may be more likely to be diagnosed with asthma, and men with COPD, regardless of their underlying condition. Furthermore, studies have shown that a smaller proportion of women compared to men are not referred for diagnostic testing for COPD, or do not receive optimal pharmacotherapy. Using data from the BC Linked Health Database and the PharmaNet database, Dr. Pat Camp is conducting an in-depth analysis of the management and health outcomes of COPD in women compared with men. The goals of Dr. Camp's research are designed to identify gender differences with respect to diagnostic test utilization, hospitalization rates and medication usage. Dr. Camp is also investigating what, if any, impact age and region of residence have on diagnostic testing, medications and hospitalizations in people with COPD. The results of Dr. Camp's research will allow for specific messages and targeted interventions to be developed that facilitate better care and improved quality of life of people living with COPD.

The development of the corticospinal tract in premature newborns: impact of early brain injury and relationship with motor abilities

Approximately eight per cent of babies in British Columbia are born prematurely (less than 37 weeks after conception), and survival rates have improved dramatically for these infants. Motor and cognitive impairments are common among children born prematurely: five to 10 per cent will exhibit motor deficits such as cerebral palsy, and up to half will experience problems with brain functions (such as learning to speak). At school age, these delays in development can become greater concerns as they may interfere with learning and social interaction. Recent studies suggest that the developmental impairment observed may be associated with abnormal development of the brain regions responsible for motor and brain functioning. Early brain abnormalities, such as white matter injury (WMI), may underlie maturational impairments of these regions. A key brain pathway of interest is the corticospinal tract, which carries voluntary motor information from the control centre of the brain (the cortex) to muscles of the body. Elysia Adams is determining whether brain abnormalities, such as WMI, in premature newborns in their early life will affect their motor and brain function. Using advanced imaging techniques with magnetic resonance imaging (MRI), she is comparing corticospinal tract development among premature babies with and without these brain abnormalities,. This will allow her to determine whether WMI affects the development of the corticospinal tract and to establish whether later motor function can be predicted by assessing the tract’s development. Ultimately, this research could lead to ways to predict brain outcome among babies born prematurely. This would allow doctors to identify motor problems earlier and provide appropriate treatments, such as physiotherapy, to improve outcomes or prevent the long-term consequences of these developmental delays.

Temporal processing deficits in developmental dyslexia – a functional MRI study

Developmental dyslexia is defined as the difficulty in learning to read, and affects between 5 and 17.5 per cent of school-age children. The cause of dyslexia is unknown, but there may be a neurobiological basis. Current diagnostic tests for dyslexia are typically conducted by grade two or three, however by this time, the child already displays significant reading difficulties and may never catch up to their peers. Developing diagnostic tests to assess or predict reading difficulties at an earlier age could allow for earlier intervention and prevention of academic and social difficulties associated with dyslexia. For many children, the main problem in dyslexia involves sound (phonological) processing. For instance, the child may not be able to link sounds to letters, or break words up into their individual sounds. Also, people with dyslexia may show deficits in visual and auditory temporal processing, which is the perception and integration of rapidly presented stimuli. For example, the child may have difficulty with determining the direction of motion or sound. It is unknown whether there is a link between reading and temporal processing skills. Marita Partanen is examining whether reading and temporal processing use overlapping brain networks, and whether these brain areas are affected in children with dyslexia. She is using functional magnetic resonance imaging (fMRI) to track brain activation in children as they complete simple tasks. If a link between reading ability and temporal processing can be established, there is potential for simpler and earlier diagnostic tests for dyslexia that assess temporal processing. Ultimately, the ability to diagnose dyslexia at a younger age may lead to new programs that can improve academic and social outcomes for people with dyslexia.

Motion perception deficits in children with amblyopia: a functional MRI investigation

Amblyopia – commonly known as “”lazy eye”” – is a developmental disorder that causes poor vision in one eye compared to the other eye. Amblyopia can arise from an inward or outward turn of the weaker eye. This prevents both eyes from working together to form one image and results in double vision. It can also arise when one eye has much better focus than the other eye. In both cases, as the brain matures it will begin to ignore the image coming from the weaker eye, eventually causing vision in that eye to deteriorate. Regardless of how amblyopia arises, the most common treatment is to place an eye patch over the good eye. This forces the maturing brain to start using the weaker eye, so that vision in this eye will “”catch up”” to the vision of the good eye. This form of treatment has been very effective in treating some cases of amblyopia, but not other cases. Currently, eye care professionals primarily use letter charts to assess how the ability to process form is affected in amblyopia. Research over the years has found that in addition to abnormalities in processing form, there are also abnormalities in motion processing. Typically, eye care professionals do not assessmotion perception, so any abnormalities in motion processing that may develop currently do not get treated. Using functional magnetic resonance imaging (fMRI), John Secen is looking at differences in brain activity between children with and without amblyopia as they perform a motion processing task. This research will improve upon the current understanding of the neural basis behind motion-processing deficits in amblyopia, and hopefully, this knowledge could lead to the development of new screening techniques so that these abnormalities in motion processing can be detected and treated.

Short term heart rate variability as an index of nociception

The brain perceives pain through the nociception system, which prompts increased activity in the autonomic nervous system (ANS). In turn, the ANS activates the sympathetic nervous system (SNS), creating a stress response in the body that includes increased respiration, blood pressure and heart rate. In sick patients, a strong stress response can cause serious injury. Anesthesiologists try to minimize the stress response during surgery by giving patients drugs that block nociception. Finding the appropriate balance can be challenging — too much anesthesia can make the patient very ill, while too little anesthesia increases the stress response. Anesthesiologists currently rely on a patient’s vital signs — pulse rate, blood pressure, temperature, and respiratory rate — to estimate the level of ANS activation and determine appropriate drug dosage. Unfortunately, these vital signs alone are not enough to estimate ANS activity, because they are often affected by other factors. Christopher Brouse is developing a nociception monitor that automatically determines the level of activation of a patient’s ANS. It will use computer algorithms that analyze very small, fast changes in the patient’s heart rate, called heart rate variability (HRV). Previous research has shown that HRV responds to ANS activation much more predictably than other vital signs do; therefore, HRV can provide a better estimate. With the data gathered from his first pilot pain study, Brouse is now developing and fine tuning a pain index that correlates with ANS activity. By accurately monitoring subtle vital signs, the nociception monitor has the potential to increase patient safety during and after surgery and reduce recovery times. It could also be used for patients recovering from surgery to gauge their pain and respond with the appropriate amount of drugs.

An application of situational awareness to child resuscitation

An estimated 23,000 preventable deaths occur annually in Canadian hospitals. One area of practice that is particularly time-sensitive and prone to errors is child resuscitation. The range of medical conditions underlying the need for child resuscitation, and the broad range in age and size of children, make this event one of the most stressful for healthcare providers. As a first responder, nurse performance is crucial to resuscitation outcomes. Situational awareness (SA) describes an individual’s awareness of what is happening, why it is happening and what will happen next. SA has been proposed as the primary basis for decision-making and performance in complex, dynamic systems and has been used extensively in high risk industries such as aviation and the military to understand how people assess threats and ensure safety within the work environment. Kimberley Shearer was previously funded by MSFHR for her early PhD work in situational awareness. She is continuing her research into the SA requirements for nurses during child resuscitation, determining what nurses need to pay attention to and anticipate in order to prevent error. She is developing a tool for objectively measuring nurse SA based on information gathered from a series of in-depth interviews with resuscitation team nurses. The tool will be validated by comparing the performance and stress levels demonstrated by novice and expert nurses during a simulated child resuscitation. Shearer’s research has implications for simulation teaching to reduce clinician error in pediatric settings. The development of an objective measure of SA can assist in the evaluation of clinician performance, facilitate understanding of differences between novices and experts, and permit testing of the effects of changes in technology on clinician performance.

Effects of Prenatal Psychotropic Medication Exposure on Critical Periods of Language Development

Psychotropic medications like benzodiazepines (tranquilizers used to control anxiety) and serotonin reuptake inhibitors (antidepressants used to treat depression) are frequently prescribed during pregnancy to manage depression and anxiety, even though these drugs have not been approved for this purpose, and the impact on infant development is unclear. These drugs increase the activity of certain chemicals in the brain that inhibit nerve cell activity. Whitney Weikum is expanding on her earlier MSFHR-funded research on language development in infants. Now Weikum is studying the effects of prenatal exposure to psychotropic drugs on critical periods of infant language development. During the first years of life, infants rapidly and almost effortlessly acquire language. There appear to be a number of discrete periods critical for acquiring language information. At birth, infants have the ability to discriminate almost all the distinctive sounds from the world’s languages. Weikum is testing infants’ responses to different language sounds at 36 weeks gestation, as newborns, and during the first year to learn whether psychotropic drugs affect cognitive and language development. The results will be compared to women who experienced depression, but did not take medication, to determine the impact of depression alone on infants’ language development. The goal is to help women and physicians make informed decisions about whether to use psychotropic medications during pregnancy.

eVENT: An expert system for detecting ventilatory events during anesthesia

Despite the best intentions of clinicians many patients suffer adverse events during their medical care. As technology becomes more sophisticated and the amount of information generated increases, the risk that something goes wrong or is missed increases. The technology, work environment and clinical work flow needs to be designed to mitigate these risks. Technology has the potential to help clinician’s with tasks that humans do not perform well, such as vigilance, and reduce risk to patients.

Dr. J Mark Ansermino is a pediatric anesthesiologist with a background in health informatics and a particular interest in patient safety. He and his team are developing an expert system that automatically detects important changes in a patient’s status in the operating room. The clinician must divide his or her time between keeping an eye on the monitors, attending to the patient, and other tasks such as teaching students and giving drugs. Important events or evolving conditions can be missed. The technology will assist the busy clinician with attending to the huge amount of information generated by the monitors and bringing the important changes to the attention of the clinician. The system can also offer advice on what should be done about these changes and information on current treatment guidelines, providing the clinician with a recommended course of action in real time.

The current emphasis is on developing rules for a few dangerous events that affect breathing. This will be expanded to address other anesthesia-related events in the operating room. In this research, the system will be evaluated in both simulated and real clinical settings to determine if it is possible for clinicians to identify and respond to critical events more rapidly and reliably. This expert system will lend itself to promoting better decision making by both less skilled or experienced anesthesiologists during training or in situations where advanced training is not available.

Team in Child and Adolescent Healthy Body Weights

At least one in four BC children and youth is overweight or obese, and many of these young people are already developing serious diseases, such as hypertension and type 2 diabetes. Preventative and therapeutic measures have not succeeded in curbing the prevalence of overweight and obese children and youth in BC and Canada. This award supports the development of a multidisciplinary team bringing together clinical, social and basic researchers. The team aims to study determinants of childhood and adolescent overweight at individual, family, community and population levels, and to develop targeted interventions that will result in sustainable outcomes and healthy body weights.