Browsing by Author "Nowak, Thomas"

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    Application of Physiological Autonomic Activity Tracking GUI and Computational Algorithms for Measuring Persistent Vagal Nerve Dysfunction After Recovery from SARS‐CoV‐2 Infection
    (Wiley, 2022) Wilson, Damen A.; Nowak, Thomas; Gupta, Anita; McKinnon, Michael; Clements, Isaac; Everett, Thomas; Powley, Terry; Ward, Matthew; Medicine, School of Medicine
    Post‐Acute Sequelae of SARS‐CoV‐2 infection (PASC) is now recognized as a constellation of symptoms such as postural hypotension, anxiety, and “brain fog” in addition to autonomic nervous system dysfunction such as tachycardia and labile hypertension. Better quantification of these conditions, specifically, autonomic nervous system dysfunction, is desired for future diagnostics, treatment modalities, and gaining a further understanding of PASC. This research has led to application of a novel autonomic activity tracking algorithm and GUI suite from previous work, see Figure 1, to study the physiological autonomic activity in six patients who had recovered from acute SARS‐CoV‐2 infection a mean of six months prior but were still experiencing symptoms. By measuring skin sympathetic nervous activity (SKNA), heart rate variability, and the cutaneous electrogastrogram (EGG), all before and after a water meal challenge, the data was fed into a custom analysis pipeline, shown in Figure 1. Each of the PASC patients were compared to a mean response of 34 healthy controls, each undergoing a 20‐minute baseline recording and another 20‐minute recording after ingestion of an 8 oz water test meal. All six patients showed significantly abnormal heart rate variability on frequency domain analysis in predominantly the low frequency (LF) and very low frequency (VLF) bands, and less so in the high frequency (HF) band, suggesting sympathetic nerve dysfunction. Three patients showed a significant decrease in SKNA while two showed a significant increase. All patients showed an abnormal cutaneous EGG. As shown in Figure 2, the temporal responses of aSKNA, VLF, LF, HF, and EGG for the PASC patients revealed that on average they were statistically different (p<0.05) from the healthy controls’ responses respectively during 98.4%, 78.4%, 86.76%, 47.9%, and 86.1% of the 40‐minute time period in testing, 20 minutes of baseline and 20 minutes after ingestion. In conclusion, we are looking at the sympathetic, parasympathetic, and enteric nervous systems synced temporally for applications with classification and further stratification of PASC based on the temporal dynamics of their autonomic nervous system mediated coordination from digestion. This shows that SARS‐CoV02 infection appears to have a significant effect on sympathetic and parasympathetic autonomic nervous system function and may be responsible for the disturbances noted in PASC. This work provides the framework and example of use for further applications in autonomic disorder physiological response exploration and furthermore can be expanded to other areas of neuromodulation.
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    Idiopathic gastroparesis is associated with specific transcriptional changes in the gastric muscularis externa
    (Wiley, 2018-04) Herring, B. Paul; Hoggatt, April M.; Gupta, Anita; Griffith, Sarah; Nakeeb, Attila; Choi, Jennifer N.; Idrees, Muhammad T.; Nowak, Thomas; Morris, David L.; Wo, John M.; Cellular and Integrative Physiology, School of Medicine
    BACKGROUND: The molecular changes that occur in the stomach that are associated with idiopathic gastroparesis are poorly described. The aim of this study was to use quantitative analysis of mRNA expression to identify changes in mRNAs encoding proteins required for the normal motility functions of the stomach. METHODS: Full-thickness stomach biopsy samples were collected from non-diabetic control subjects who exhibited no symptoms of gastroparesis and from patients with idiopathic gastroparesis. mRNA was isolated from the muscularis externa and mRNA expression levels were determined by quantitative reverse transcriptase (RT)-PCR. KEY RESULTS: Smooth muscle tissue from idiopathic gastroparesis patients had decreased expression of mRNAs encoding several contractile proteins, such as MYH11 and MYLK1. Conversely, there was no significant change in mRNAs characteristic of interstitial cells of Cajal (ICCs) such as KIT or ANO1. There was also a significant decrease in mRNA-encoding platelet-derived growth factor receptor α (PDGFRα) and its ligand PDGFB and in Heme oxygenase 1 in idiopathic gastroparesis subjects. In contrast, there was a small increase in mRNA characteristic of neurons. Although there was not an overall change in KIT expression in gastroparesis patients, KIT expression showed a significant correlation with gastric emptying whereas changes in MYLK1, ANO1 and PDGFRα showed weak correlations to the fullness/satiety subscore of patient assessment of upper gastrointestinal disorder-symptom severity index scores. CONCLUSIONS AND INFERENCES: Our findings suggest that idiopathic gastroparesis is associated with altered smooth muscle cell contractile protein expression and loss of PDGFRα+ cells without a significant change in ICCs.
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    Relationships of Intestinal Lactase and the Small Intestinal Microbiome with Symptoms of Lactose Intolerance and Intake in Adults
    (Springer, 2022) Jansson-Knodell, Claire L.; Krajicek, Edward J.; Ramakrishnan, Monica; Rogers, Nicholas A.; Siwiec, Robert; Bohm, Matt; Nowak, Thomas; Wo, John; Lockett, Carolyn; Xu, Huiping; Savaiano, Dennis A.; Shin, Andrea; Medicine, School of Medicine
    Background: Approximately two-thirds of adults are genetically predisposed to decreased lactase activity after weaning, putting them at risk of lactose intolerance. However, symptoms are a poor marker of lactose maldigestion. Aims: We assessed association between self-reported lactose intolerance and intestinal lactase, lactose intake, and the small intestinal microbiome. Methods: Patients 18-75 years presenting for upper endoscopy were recruited prospectively. Observational study participants completed a lactose intolerance symptom questionnaire and reported lactose intake. Post-bulbar biopsies were obtained to measure lactase activity and assess the small intestinal mucosal microbiome. We compared intestinal lactase between patients with and without lactose intolerance. We assessed associations between lactose intolerance symptoms and lactase and lactose intake. We examined associations of small bowel microbial composition with self-reported lactose intolerance and symptoms. Results: Among 34 patients, 23 (68%) reported lactose intolerance. Those with lactose intolerance had higher total symptom scores, more frequent bowel urgency, and more bowel movements after consuming dairy. The proportion of individuals with abnormal lactase activity did not differ by lactose intolerance status. Median lactase levels were correlated with total lactose intolerance symptom scores (p = 0.038) and frequency of bowel urgency (p = 0.012). Daily lactose intake did not differ between groups. In 19 patients, we observed significant associations of small intestinal microbiome beta diversity with stool consistency after consuming dairy (p = 0.03). Conclusions: Intestinal lactase is associated with lactose intolerance symptoms and bowel urgency in adults but does not distinguish the clinical phenotype entirely. Studying other contributing factors (microbiota, diet) may further clarify the pathophysiology of lactose intolerance.