The aspiration of oral and gastric substances is a well-known risk for ventilator associated pneumonia (VAP) in the intubated, mechanically ventilated (MV), patient of the intensive care unit (ICU) population. The gastric biomarker pepsin and the oral biomarker salivary amylase have been identified as evidence of aspiration prior to the manifestation of acute pulmonary illness. In an effort to decrease the risk for aspiration, several evidence based nursing practices are in place. Actions include 30 degree head of the bed positioning, oral care, suctioning, and circuit change interval protocols, as well as the administration of medication with the objective of reducing acid reflux. Additional recommendations concern the type of endotracheal tube (ETT) used to ventilate the intubated patient. The continuous subglottic suctioning endotracheal tube (CSS-ETT) features an additional port which continually suctions secretions that accumulate above the inflated endotracheal cuff. Patients with standard endotracheal tubes (S-ETT) receive manual, as needed suctioning of accumulated secretions in the mouth and the oropharynx per agency protocol. Research of the critical care population has demonstrated a decreased instance of VAP using CSS-ETT as compared to S-ETT utilization. This study sought to compare the incidence of the biomarkers pepsin and salivary amylase in the suctioned oral and tracheal secretions of patients with S-ETT compared to patients with CSS-ETT. Part of the protocol of a descriptive, comparative study of the clinical indicators for suctioning established the collection of the paired suctioned oral and tracheal aspirates. Those collected aspirates were analyzed for a pilot study of pepsin and amylase analysis. This study compares the incidence of aspirates in oral and tracheal secretions by endotracheal tube type.; The intention of this study was that it would assist in demonstrating beneficial aspects of the selection of the CSS-ETT. It is considered that further investigation with a larger population group could add statistical significance.; Tracheal aspirates were obtained with a closed tracheal suction device while oral secretions were obtained with a suction catheter designed to reach the oropharynx. Biomarkers assayed were the gastric marker pepsin and the oropharyngeal marker salivary amylase. Assays of pepsin and salivary amylase were performed using standard procedures in a specialty diagnostic laboratory. Specimens were obtained from 11 subjects: 8 male and 3 female. The majority were Caucasian (n=9), had a CSS-ETT (n=8), were on mechanical ventilation in the synchronized intermittent mandatory ventilation mode, and on tube feedings (n=9) located in the stomach (n=7). The mean age was 56 years. Feeding tubes were placed in 9 patients, and the majority of the tubes were Dobbhoff. Pepsin was found in the oral secretions of 62.5% (n = 5) of the CSS-ETT subjects, while 50.0% (n = 4) had pepsin in the tracheal aspirate. Pepsin was found in the oral secretions of 66.7% (n = 2) of the S-ETT subjects, and 66.7% (n = 2) had pepsin in their tracheal aspirate. All subjects of both groups (n = 11) had oral salivary amylase detected. Salivary amylase was detected in the tracheal aspirate of 100% (n = 3) of the S-ETT subjects versus 62.5% (n = 5) in CSS-ETT group. Based on the results of this study, there was a reduction in the number of subjects who had oral compared to tracheal aspirate pepsin in the CSS-ETT group (n = 5 oral versus n = 4 tracheal) tube type. The S-ETT group had equal number of subjects with oral (n = 2) and tracheal pepsin detected (n = 2). However, the results when comparing the S-ETT and the CSS-ETT groups were not statistically significant (p = 0.898 pepsin oral and 0.621 tracheal pepsin). There may be clinical significance. It appears that the CSS-ETT was beneficial in that group; two fewer subjects had pepsin in their tracheal aspirate (n = 5 oral versus n = 4 tracheal aspirate pepsin).

No / In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not only psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/tumor necrosis factor-α (TNFα)-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses, IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, because of its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.

No / The remote robotic exploration of extraterrestrial scenarios for evidence of biological colonization in 'search for life' missions using Raman spectroscopy is critically dependent on two major factors: firstly, the Raman spectral recognition of characteristic biochemical spectral signatures in the presence of mineral matrix features; and secondly, the positive unambiguous identification of molecular biomaterials which are indicative of extinct or extant life. Both of these factors are considered here: the most important criterion is the clear definition of which biochemicals truly represent biomarkers, whose presence in the planetary geological record from an analytical astrobiological standpoint will unambiguously be indicative of life as recognized from its remote instrumental interrogation. Also discussed in this paper are chemical compounds which are associated with living systems, including biominerals, which may not in themselves be definitive signatures of life processes and origins but whose presence provides an indicator of potential life-bearing matrices.

Yes / Personalized medicine through Pharmacogenomics: choosing the right drug, and the right dose, for the right patients based on patient’s genetic makeup-is gradually being realised in Western countries. Yet, the practice of pharmacogenomics in Asian countries lags behind that of the West, but the medical needs for pharmacogenomics are expected to surge as better patient care is demanded in Asia. As next-generation sequencing technology advances quickly, previous technical challenges for performing pharmacogenomic studies or practices in Asia have been mostly resolved. What is lacking in Asia is an effective model of community-wide pharmacogenomics. On the delivery front, pharmacists, the drug and dosing professionals, can potentially be the main healthcare providers for pharmacogenomic services in Asia. The first large “Genomics for Precision Drug Therapy in the Community Pharmacy” in Canada, which is close to its completion, has successfully identified community pharmacists as key contact professionals for smooth facilitation and implementation of pharmacogenomics for personalized medication. It is anticipated that Asian pharmacists, with appropriate training, can have the capacity to provide expert pharmacogenomic supports for both physicians and patients in Asia. / The School of Biomedical Sciences Start-up Fund, the Chinese University of Hong Kong, the General Research Fund (#17114814; #17121616), the Theme-based Research Scheme (T12-401/13-R), Research Grant Council, Hong Kong, as well as the Hong Kong Cancer Fund, Hong Kong.

Yes / Background: This study investigated predictors of response to topical diphenylyclopropenone (DPCP) immunotherapy in patients with alopecia areata (AA). Objective: To identify predictors of response, or resistance, to treatment for AA through clinical observations and serum tests. Methods: Eighty four AA patients were treated with DPCP. Serum cytokine levels were measured in 33 AA patients pre- and post-treatment, and in 18 healthy controls, using ELISA assays. Results: Of patients, 56.1% responded to DPCP with satisfactory hair regrowth; the response rate was negatively correlated with hair loss extent. Before DPCP treatment, higher serum IFN-γ and IL-12 cytokine levels were observed in AA patients compared to healthy controls. Non-responders to DPCP had significantly elevated serum IL-4 pre-treatment (3.07 fold higher) and lower IL-12 levels compared with responders. After DPCP treatment, non-responders had persistently high IL-4, increased IL-12, negligible decrease in IFN-γ and decreased IL-10. Post-treatment DPCP responders exhibited significantly decreased IFN-γ and IL-12, and increased IL-4 and IL-10. Development of adverse side-effects was significantly associated with higher pre-treatment serum IgE levels. Limitations: A small number of subjects were evaluated. Conclusions: Potentially, elevated pre-treatment serum levels of IL-4 and IL-12 can be used as unfavorable and favorable predictors of DPCP therapeutic effect, respectively. In addition, pre-treatment elevated serum total IgE may predict increased risk for severe adverse side-effects to DPCP application. Whether serum cytokine expression levels can be used as predictors of response to other forms of treatment is unknown, but it may warrant investigation in the development of personalized treatments for AA. / This work is supported by the National Natural Science Foundation of China (81573066) and Natural Science Foundation of Guangdong Province (2014A030313098) to Xingqi Zhang.

Emotion processing and regulatory deficits have been well established in individuals diagnosed with bipolar disorder (BD). Both structural and functional neural deficits have been associated with the presence of psychiatric symptoms in BD. In Chapter 2, we reviewed cortical thickness deficits found in patients with BD. It is unclear however, how early these deficits appear; whether they contribute to risk, or whether these deficits develop as a consequence of the onset of symptoms. To address this, many researchers have turned to high-risk offspring populations. These high-risk offspring are at much greater risk of developing BD by virtue of having a parent diagnosed with BD. Moreover, the presence of anxiety, depression or ADHD related symptoms in this population suggest these children are at even greater risk to develop BD. By comparing high-risk offspring with and without the symptoms can help to elicudate neural correlates associated with risk and resilience for BD. It was the aim of this thesis research to investigate the behavioural, structural and functional correlates of risk. Specifically, presented in this thesis, we compared the gray matter integrity, through volume (Chapter 3) and cortical thickness (Chapter 4) techniques, in symptomatic and asymptomatic high-risk offspring to healthy children of healthy parents. We also compared the ability of these offspring to perform an emotion-labelling task (Chapter 5) and engage in emotional conflict monitoring and conflict adaptation during an fMRI scan (Chapter 6). Altogether, our results provide evidence for the presence of gray matter volume, emotion labelling, and conflict monitoring and conflict adaptation functional deficits in high-risk offspring compared to healthy children of healthy parents. With the exception of cortical thickness, we found that the deficits between symptomatic and asymptomatic high-risk offspring were comparable. This suggests that behavioural, structural and functional deficits may reflect neural correlates of risk and are not associated with the presence of symptoms. / Thesis / Doctor of Philosophy (PhD)

Objective: Alcohol use disorder (AUD) remains a leading cause of worldwide mortality and morbidity. The development of neuroanatomical biomarkers offers the potential of novel clinical indicators to guide prevention, early diagnosis, and treatment. Methods: In 76 participants with DSM-5 diagnosed AUD (Mage = 35.75; 51.3% female) and 79 controls (Mage = 34.71; 59.5% female), we utilized magnetic resonance imaging (MRI) to investigate four novel measures: hippocampal and amygdalar subregion volumes, sulcal morphology (SM), and fractal dimensionality (FD). MRI processing, segmentation, and SM and FD quantification were completed using FreeSurfer v6.0 and v7.0, and MATLAB toolboxes, respectively. A significance value of p < .05 was employed for analysis and sex, age, and intracranial volume were included as covariates. Results: Volumes of the right presubiculum, subiculum, and molecular layer head; left lateral and accessory basal nuclei; and corticoamygdaloid transition area were significantly lower in AUD participants relative to healthy controls. Widths of the left occipito-temporal, right middle occipital and lunate, and right marginal part of the cingulate sulci and depth of the post-central sulci were significantly increased in AUD participants relative to controls. Finally, decreased left caudate, left thalamus, right putamen and right pallidum FD and greater inferior lateral and third ventricle FD were observed in AUD participants relative to controls. Each novel measure’s reliability was assessed using test-retest data from the Human Connectome Project and indicated high reliability with median intraclass correlations of .93, .91, .88, and .93 for the hippocampal subfields, amygdalar nuclei, SM, and FD, respectively. Conclusion: These results indicate selectively decreased hippocampal and amygdala subregion volume, increased sulcal depth and width, and differences in FD as promising neuroanatomical biomarkers for AUD. / Thesis / Master of Health Sciences (MSc)

No description available.

Objective: To evaluate whether abnormal concentrations in cardiac and inflammatory biomarkers could predict reductions in left ventricular ejection fraction (LVEF) for cancer patients undergoing curative treatment. Materials and Methods: Longitudinal testing was performed for high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), heart-type fatty acid binding protein (H-FABP) and C-reactive protein (CRP) in HER2+ breast cancer (BC) patients receiving adjuvant trastuzumab treatment (n=22) and in lymphoma patients treated with radiotherapy (n=4). Sex-specific and overall upper limit of normal (ULN) cutoffs were used to identify abnormal results with a reduction in LVEF (<50% and decrease of ≥10% from baseline) indicative of cardiotoxicity. A secondary analysis was performed on the BC patients with normal LVEFs (n=12 with baseline prior to chemotherapy through to 6-months on trastuzumab) with 15 blood collections spaced between 6- and 254-days post-baseline LVEF measurement. Results: A majority of the BC patients had evidence of myocardial injury (hs-cTnI >female ULN=90%) or myocardial dysfunction (NT-proBNP >overall ULN=91%) at any timepoint with fewer patients having abnormal CRP or H-FABP concentrations (H-FABP >ULN=14%; CRP >ULN=45%). Myocardial injury and dysfunction were most evident during the first two cycles of trastuzumab treatment, with myocardial injury also evident during this early timeframe in the female lymphoma patients (3 with hs-cTnI >ULN). In the 12 patients who completed trastuzumab with normal LVEFs (median=60% at 6-months), myocardial injury (hs-cTnI >ULN) and dysfunction (NT-proBNP >ULN) was evident in >50% of patients. Four of the 22 patients did develop cardiotoxicity, but there was no difference in biomarker concentrations between patients with or without cardiotoxicity. Conclusion: The use of the recommended ULN cutoffs identified myocardial injury and dysfunction in a majority of cancer patients in this setting. Biomarker assessments did not relate to cardiac functional imaging studies. Future studies are warranted to assess different cutoffs or biomarker combinations for predicting cardiotoxicity. / Thesis / Master of Science (MSc)

The discovery of cancer biomarkers is crucial in the clinical setting to facilitate early diagnosis and treatment, thereby increasing survival rates. Proteomic technologies with mass spectrometry detection (MS) have the potential to affect the entire spectrum of cancer research by identifying these biomarkers. Simultaneously, microfabricated devices have evolved into ideal analysis platforms for minute amounts of sample, with promising applications for proteomic investigations and future biomarker screening. This thesis reports on the analysis of the proteomic constituents of the MCF7 breast cancer cell line using a shotgun 2-D strong cationic exchange/reversed phase liquid chromatography electrospray ionization tandem mass spectrometry (SCX/RP-LC-ESI-MS/MS) protocol. A series of optimization strategies were performed to improve the LC-MS experimental set-up, sample preparation, data acquisition and database searching parameters, and to enable the detection and confident identification of a large number of proteins. Over ~4,500 proteins were identified using conventional filtering parameters, and >2000 proteins using a combination of filters and p-value sorting. Of these, ~1,950 proteins had p<0.001 (~90%) and more than half were identified by &#8805; 2 unique peptides. About 220 proteins were functionally involved in cancer related cellular processes, and over 100 proteins were previously described in the literature as potential cancer markers. Biomarkers such as PCNA, cathepsin D, E-cadherin, 14-3-3-sigma, antigen Ki-67, TP53RK, and calreticulin were identified. These data were generated by subjecting to mass spectrometric analysis ~42 µg of protein digest, analyzing 16 SCX peptide fractions, and interpreting ~55,000 MS2 spectra. Total MS time required for analysis was 40 h. Selective SCX fractions were also analyzed by using a microfluidic LC platform. The performance of the microchip LC was comparable to that obtained with bench-top instrumentation when similar experimental conditions were used. The identification of 5 cancer biomarkers was enabled by using the microchip LC platform. Furthermore, this device was also capable to analyze phosphopeptides. / Master of Science